Abstract
Glioblastoma multiform (GBM) is the most common primary brain tumor with a poor prognosis and few therapeutic choices. In vivo, tumor models are useful for enhancing knowledge of underlying GBM pathology and developing more effective therapies/agents at the preclinical level, as they recapitulate human brain tumors. The C6 glioma cell line has been one of the most widely used cell lines in neuro-oncology research as they produce tumors that share the most similarities with human GBM regarding genetic, invasion, and expansion profiles and characteristics. This review provides an overview of the distinctive features and the different animal models produced by the C6 cell line. We also highlight specific applications of various C6 in vivo models according to the purpose of the study and offer some technical notes for more convenient/repeatable modeling. This work also includes novel findings discovered in our laboratory, which would further enhance the feasibility of the model in preclinical GBM investigations.
-
Research ethics: Animal studies were approved by the Ethics Committee of Tarbiat Modares University (IR.MODARES.REC.1400.064), and (IR.MODARES.REC.1400.101).
-
Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission. Mohammad Hossein Pourgholami devised the conceptual idea of the article, supervised and completed the manuscript. Safura Pournajaf wrote the manuscript. Nastaran Afsordeh assisted with the writing of the manuscript.
-
Competing interests: The authors state no conflict of interest.
-
Research funding: None declared.
-
Data availability: Not applicable.
References
Akter, F., Simon, B., de Boer, N.L., Redjal, N., Wakimoto, H., and Shah, K. (2021). Pre-clinical tumor models of primary brain tumors: challenges and opportunities. Biochim. Biophys. Acta Rev. Cancer 1875: 188458, https://doi.org/10.1016/j.bbcan.2020.188458.Search in Google Scholar PubMed PubMed Central
Amberger, V.R., Hensel, T., Ogata, N., and Schwab, M. (1998). Spreading and migration of human glioma and rat C6 cells on central nervous system myelin in vitro is correlated with tumor malignancy and involves a metalloproteolytic activity. Cancer Res. 58: 149–158.Search in Google Scholar
Arrieta, O., Guevara, P., Escobar, E., García-Navarrete, R., Pineda, B., and Sotelo, J. (2005). Blockage of angiotensin II type I receptor decreases the synthesis of growth factors and induces apoptosis in C6 cultured cells and C6 rat glioma. Br. J. Cancer 92: 1247–1252, https://doi.org/10.1038/sj.bjc.6602483.Search in Google Scholar PubMed PubMed Central
Arrieta, O., Guevara, P., Reyes, S., Palencia, G., Rivera, E., and Sotelo, J. (2001). Paradoxical effect of aspirin on the growth of C6 rat glioma and on time of development of ENU-induced tumors of the nervous system. J. Cancer Res. Clin. Oncol 127: 681–686, https://doi.org/10.1007/s004320100267.Search in Google Scholar PubMed
Arrieta, O., Guevara, P., Tamariz, J., Rembao, D., Rivera, E., and Sotelo, J. (2002). Antiproliferative effect of thalidomide alone and combined with carmustine against C6 rat glioma. Int. J. Exp. Pathol 83: 99–104, https://doi.org/10.1046/j.1365-2613.2002.00219.x.Search in Google Scholar PubMed PubMed Central
Asai, A., Miyagi, Y., Sugiyama, A., Gamanuma, M., Hong, S.I., Takamoto, S., Nomura, K., Matsutani, M., Takakura, K., and Kuchino, Y. (1994). Negative effects of wild-type p53 and s-Myc on cellular growth and tumorigenicity of glioma cells: implication of the tumor suppressor genes for gene therapy. J. Neurooncol. 19: 259–268, https://doi.org/10.1007/bf01053280.Search in Google Scholar PubMed
Assanah, M., Lochhead, R., Ogden, A., Bruce, J., Goldman, J., and Canoll, P. (2006). Glial progenitors in adult white matter are driven to form malignant gliomas by platelet-derived growth factor-expressing retroviruses. J. Neurosci. 26: 6781–6790, https://doi.org/10.1523/jneurosci.0514-06.2006.Search in Google Scholar
Atzori, M.G., Tentori, L., Ruffini, F., Ceci, C., Bonanno, E., Scimeca, M., Lacal, P.M., and Graziani, G. (2018). The anti-vascular endothelial growth factor receptor-1 monoclonal antibody D16F7 inhibits glioma growth and angiogenesis in vivo. J. Pharmacol. Exp. Ther. 364: 77–86, https://doi.org/10.1124/jpet.117.244434.Search in Google Scholar PubMed
Auer, R.N., Maestro, R.F.D., and Anderson, R. (1981). A simple and reproducible experimental in vivo glioma model. Can J. Neurol. Sci. 8: 325–331, https://doi.org/10.1017/s0317167100043468.Search in Google Scholar PubMed
Ayala-Domínguez, L., Pérez-Cárdenas, E., Avilés-Salas, A., Medina, L.A., Lizano, M., and Brandan, M.E. (2020). Quantitative imaging parameters of contrast-enhanced micro-computed tomography correlate with angiogenesis and necrosis in a subcutaneous C6 glioma model. Cancers 12: 3417, https://doi.org/10.3390/cancers12113417.Search in Google Scholar PubMed PubMed Central
Ayers, G.D., McKinley, E.T., Zhao, P., Fritz, J.M., Metry, R.E., Deal, B.C., Adlerz, K.M., Coffey, R.J., and Manning, H.C. (2010). Volume of preclinical xenograft tumors is more accurately assessed by ultrasound imaging than manual caliper measurements. J. Ultrasound Med. 29: 891–901, https://doi.org/10.7863/jum.2010.29.6.891.Search in Google Scholar PubMed PubMed Central
Barth, R.F. and Kaur, B. (2009). Rat brain tumor models in experimental neuro-oncology: the C6, 9L, T9, RG2, F98, BT4C, RT-2 and CNS-1 gliomas. J. Neurooncol. 94: 299–312, https://doi.org/10.1007/s11060-009-9875-7.Search in Google Scholar PubMed PubMed Central
Benda, P., Lightbody, J., Sato, G., Levine, L., and Sweet, W. (1968). Differentiated rat glial cell strain in tissue culture. Science 161: 370–371, https://doi.org/10.1126/science.161.3839.370.Search in Google Scholar PubMed
Bernstein, J.J., Goldberg, W.J., Laws, E.R.Jr., Conger, D., Morreale, V., and Wood, L.R. (1990). C6 glioma cell invasion and migration of rat brain after neural homografting: ultrastructure. Neurosurgery 26: 622–628, https://doi.org/10.1227/00006123-199004000-00010.Search in Google Scholar
Beutler, A.S., Banck, M.S., Wedekind, D., and Hedrich, H.J. (1999). Tumor gene therapy made easy: allogeneic major histocompatibility complex in the C6 rat glioma model. Hum. Gene Ther. 10: 95–101, https://doi.org/10.1089/10430349950019228.Search in Google Scholar PubMed
Biasibetti, E., Valazza, A., Capucchio, M.T., Annovazzi, L., Battaglia, L., Chirio, D., Gallarate, M., Mellai, M., Muntoni, E., Peira, E., et al.. (2017). Comparison of allogeneic and syngeneic rat glioma models by using MRI and histopathologic evaluation. Comp. Med. 67: 147–156.Search in Google Scholar
Caballero Navarro, A., Conde Guerri, B., Sinues Porta, E., Boada Apilluelo, E., and Alcalá Arellano, A. (1992). In vitro analysis of the cellular resistance to chemotherapeutic BCNU. Histol. Histopathol. 7: 347–351.Search in Google Scholar
Cai, W.-L. and Hong, G.-B. (2018). Quantitative image analysis for evaluation of tumor response in clinical oncology. Chronic Dis. Transl. Med. 4: 18–28, https://doi.org/10.1016/j.cdtm.2018.01.002.Search in Google Scholar PubMed PubMed Central
Cao, M., Mao, J., Duan, X., Lu, L., Zhang, F., Lin, B., Chen, M., Zheng, C., Zhang, X., and Shen, J. (2018). In vivo tracking of the tropism of mesenchymal stem cells to malignant gliomas using reporter gene-based MR imaging. Int. J. Cancer 142: 1033–1046, https://doi.org/10.1002/ijc.31113.Search in Google Scholar PubMed
Caragher, S., Chalmers, A.J., and Gomez-Roman, N. (2019). Glioblastoma’s next top model: novel culture systems for brain cancer radiotherapy research. Cancers 11: 44, https://doi.org/10.3390/cancers11010044.Search in Google Scholar PubMed PubMed Central
Chintala, S.K., Tonn, J.C., and Rao, J.S. (1999). Matrix metalloproteinases and their biological function in human gliomas. Dev. Neurosci. 17: 495–502, https://doi.org/10.1016/s0736-5748(99)00010-6.Search in Google Scholar PubMed
Chiu, K.M., Harris, J.E., Kroin, J.S., Slayton, W., and Braun, D.P. (1983). The immunological response of Wistar rats to the intracranially implanted C-6 glioma cell line. J. Neurooncol. 1: 365–372, https://doi.org/10.1007/bf00165720.Search in Google Scholar PubMed
Coomber, B.L., Stewart, P.A., Hayakawa, E.M., Farrell, C.L., and Del Maestro, R.F. (1988). A quantitative assessment of microvessel ultrastructure in C6 astrocytoma spheroids transplanted to brain and to muscle. J. Neuropathol. Exp. Neurol. 47: 29–40, https://doi.org/10.1097/00005072-198801000-00004.Search in Google Scholar PubMed
Dagıstan, Y., Karaca, I., Bozkurt, E.R., Ozar, E., Yagmurlu, K., Toklu, A., and Bilir, A. (2012). Combination hyperbaric oxygen and temozolomide therapy in C6 rat glioma model. Acta Cir. Bras. 27: 383–387, https://doi.org/10.1590/s0102-86502012000600005.Search in Google Scholar PubMed
de Vasconcelos, A., de Moura, L.R., Pedra, N.S., Bona, N.P., Soares, M.S.P., da Silva Marques, M., Horn, A.P., Spohr, L., Spanevello, R.M., Stefanello, F.M., et al.. (2022). Thiazolidine-2,4-dione derivative exhibits antitumoral effect and reverts behavioral and metabolic changes in a model of glioblastoma. Metab. Brain. Dis. 37: 2053–2059, https://doi.org/10.1007/s11011-022-01005-5.Search in Google Scholar PubMed
Doblas, S., He, T., Saunders, D., Pearson, J., Hoyle, J., Smith, N., Lerner, M., and Towner, R.A. (2010). Glioma morphology and tumor-induced vascular alterations revealed in seven rodent glioma models by in vivo magnetic resonance imaging and angiography. J. Magn. Reson. Imaging 32: 267–275, https://doi.org/10.1002/jmri.22263.Search in Google Scholar PubMed PubMed Central
Du, Z., Jia, D., Liu, S., Wang, F., Li, G., Zhang, Y., Cao, X., Ling, E.A., and Hao, A.J.G. (2009). Oct4 is expressed in human gliomas and promotes colony formation in glioma cells. Glia 57: 724–733, https://doi.org/10.1002/glia.20800.Search in Google Scholar PubMed
Fan, R., Chuan, D., Hou, H., Chen, H., Han, B., Zhang, X., Zhou, L., Tong, A., Xu, J., and Guo, G. (2019). Development of a hybrid nanocarrier-recognizing tumor vasculature and penetrating the BBB for glioblastoma multi-targeting therapy. Nanoscale 11: 11285–11304, https://doi.org/10.1039/c9nr01320b.Search in Google Scholar PubMed
Fan, Y., Cui, Y., Hao, W., Chen, M., Liu, Q., Wang, Y., Yang, M., Li, Z., Gong, W., Song, S., et al.. (2021). Carrier-free highly drug-loaded biomimetic nanosuspensions encapsulated by cancer cell membrane based on homology and active targeting for the treatment of glioma. Bioact. Mater. 6: 4402–4414, https://doi.org/10.1016/j.bioactmat.2021.04.027.Search in Google Scholar PubMed PubMed Central
Fratantonio, D., Molonia, M.S., Bashllari, R., Muscarà, C., Ferlazzo, G., Costa, G., Saija, A., Cimino, F., and Speciale, A. (2019). Curcumin potentiates the antitumor activity of Paclitaxel in rat glioma C6 cells. Phytomedicine 55: 23–30, https://doi.org/10.1016/j.phymed.2018.08.009.Search in Google Scholar PubMed
Fridman, R., Benton, G., Aranoutova, I., Kleinman, H.K., and Bonfil, R.D. (2012). Increased initiation and growth of tumor cell lines, cancer stem cells and biopsy material in mice using basement membrane matrix protein (Cultrex or Matrigel) co-injection. Nat. Protoc. 7: 1138–1144, https://doi.org/10.1038/nprot.2012.053.Search in Google Scholar PubMed
Fu, Y., Huang, R., Zheng, Y., Zhang, Z., and Liang, A. (2011). Glioma-derived mutations in isocitrate dehydrogenase 2 beneficial to traditional chemotherapy. Biochem. Biophys. Res. Commun. 410: 218–223, https://doi.org/10.1016/j.bbrc.2011.05.108.Search in Google Scholar PubMed
Fu, Y., Zheng, Y., Li, K., Huang, R., Zheng, S., An, N., and Liang, A. (2012). Mutations in isocitrate dehydrogenase 2 accelerate glioma cell migration via matrix metalloproteinase-2 and 9. Biotechnol. Lett. 34: 441–446, https://doi.org/10.1007/s10529-011-0800-8.Search in Google Scholar PubMed
Garcia, J.H., Jain, S., and Aghi, M.K. (2021). Metabolic drivers of invasion in glioblastoma. Front. Cell Dev. Biol. 9: 683276, https://doi.org/10.3389/fcell.2021.683276.Search in Google Scholar PubMed PubMed Central
Giakoumettis, D., Kritis, A., and Foroglou, N. (2018). C6 cell line: the gold standard in glioma research. Hippokratia 22: 105–112.Search in Google Scholar
Gieryng, A., Pszczolkowska, D., Bocian, K., Dabrowski, M., Rajan, W.D., Kloss, M., Mieczkowski, J., and Kaminska, B. (2017). Immune microenvironment of experimental rat C6 gliomas resembles human glioblastomas. Sci. Rep. 7: 17556, https://doi.org/10.1038/s41598-017-17752-w.Search in Google Scholar PubMed PubMed Central
Glantz, M.J., Choy, H., Kearns, C.M., Mills, P.C., Wahlberg, L.U., Zuhowski, E.G., Calabresi, P., and Egorin, M.J. (1995). Paclitaxel disposition in plasma and central nervous systems of humans and rats with brain tumors. J. Natl. Cancer Inst. 87: 1077–1081, https://doi.org/10.1093/jnci/87.14.1077.Search in Google Scholar PubMed
Grobben, B., De Deyn, P.P., and Slegers, H. (2002). Rat C6 glioma as experimental model system for the study of glioblastoma growth and invasion. Cell Tissue Res. 310: 257–270, https://doi.org/10.1007/s00441-002-0651-7.Search in Google Scholar PubMed
Guerin, E., Man, S., Xu, P., and Kerbel, R.S. (2013). A model of postsurgical advanced metastatic breast cancer more accurately replicates the clinical efficacy of antiangiogenic drugs. Cancer Res. 73: 2743–2748, https://doi.org/10.1158/0008-5472.can-12-4183.Search in Google Scholar PubMed PubMed Central
Guevara, P. and Sotelo, J. (1999). C6 rat glioma grown into the peritoneal cavity, a large source of tumoral cells for subcutaneous transplant of glioma. J. Neurooncol. 44: 91–92, https://doi.org/10.1023/a:1006112422132.10.1023/A:1006112422132Search in Google Scholar PubMed
Haddad, A.F., Young, J.S., Amara, D., Berger, M.S., Raleigh, D.R., Aghi, M.K., and Butowski, N.A. (2021). Mouse models of glioblastoma for the evaluation of novel therapeutic strategies. Neurooncol. Adv. 3: vdab100, https://doi.org/10.1093/noajnl/vdab100.Search in Google Scholar PubMed PubMed Central
Han, S., Lee, Y., and Lee, M. (2021). Biomimetic cell membrane-coated DNA nanoparticles for gene delivery to glioblastoma. J. Control. Release 338: 22–32, https://doi.org/10.1016/j.jconrel.2021.08.021.Search in Google Scholar PubMed
Haydar, N., Alyousef, K., Alanan, U., Issa, R., Baddour, F., Al-shehabi, Z., and Al-janabi, M.H. (2022). Role of Magnetic Resonance Imaging (MRI) in grading gliomas comparable with pathology: a cross-sectional study from Syria. Ann. Med. Surg 82: 104679, https://doi.org/10.1016/j.amsu.2022.104679.Search in Google Scholar PubMed PubMed Central
Hetze, S., Sure, U., Schedlowski, M., Hadamitzky, M., and Barthel, L. (2021). Rodent models to analyze the glioma microenvironment. ASN Neuro. 13: 17590914211005074, https://doi.org/10.1177/17590914211005074.Search in Google Scholar PubMed PubMed Central
Hirai, N., Watabe, T., Nagamori, S., Wiriyasermkul, P., Tanaka, Y., Romanov, V., Naka, S., Kanai, Y., Liu, Y., Tani, N., et al.. (2020). Evaluation of D-isomer of (18)F-FBPA for oncology PET focusing on the differentiation of glioma and inflammation. Asia Ocean J. Nucl. Med. Biol. 8: 102–108, https://doi.org/10.22038/AOJNMB.2020.47399.1321.Search in Google Scholar PubMed PubMed Central
Hughes, C.S., Postovit, L.M., and Lajoie, G.A. (2010). Matrigel: a complex protein mixture required for optimal growth of cell culture. Proteomics 10: 1886–1890, https://doi.org/10.1002/pmic.200900758.Search in Google Scholar PubMed
Hung, C.F. (2000). Effects of carmustine and lomustine on arylamine N-acetyltransferase activity and 2-aminofluorene-DNA adducts in rat glial tumor cells. Neurochem. Res. 25: 845–851, https://doi.org/10.1023/a:1007573609158.10.1023/A:1007573609158Search in Google Scholar PubMed
Ireson, C.R., Alavijeh, M.S., Palmer, A.M., Fowler, E.R., and Jones, H.J. (2019). The role of mouse tumour models in the discovery and development of anticancer drugs. Br. J. Cancer 121: 101–108, https://doi.org/10.1038/s41416-019-0495-5.Search in Google Scholar PubMed PubMed Central
Junttila, M.R. and de Sauvage, F.J. (2013). Influence of tumour micro-environment heterogeneity on therapeutic response. Nature 501: 346–354, https://doi.org/10.1038/nature12626.Search in Google Scholar PubMed
Kato, H., Huang, X., Kadonaga, Y., Katayama, D., Ooe, K., Shimoyama, A., Kabayama, K., Toyoshima, A., Shinohara, A., Hatazawa, J., et al.. (2021). Intratumoral administration of astatine-211-labeled gold nanoparticle for alpha therapy. J. Nanobiotechnol. 19: 223, https://doi.org/10.1186/s12951-021-00963-9.Search in Google Scholar PubMed PubMed Central
Kaye, A.H., Morstyn, G., Gardner, I., and Pyke, K. (1986). Development of a xenograft glioma model in mouse brain. Cancer Res. 46: 1367–1373.Search in Google Scholar
Kefayat, A., Ghahremani, F., Motaghi, H., and Amouheidari, A. (2019). Ultra-small but ultra-effective: folic acid-targeted gold nanoclusters for enhancement of intracranial glioma tumors’ radiation therapy efficacy. Nanomedicine 16: 173–184, https://doi.org/10.1016/j.nano.2018.12.007.Search in Google Scholar PubMed
Kim, J., Lee, J.W., Kim, S.I., Choi, Y.J., Lee, W.K., Jeong, M.J., Cha, S.H., Lee, H.J., Chun, W., and Kim, S.S. (2011). Thrombin-induced migration and matrix metalloproteinase-9 expression are regulated by MAPK and PI3K pathways in C6 glioma cells. Korean J. Physiol. Pharmacol. 15: 211–216, https://doi.org/10.4196/kjpp.2011.15.4.211.Search in Google Scholar PubMed PubMed Central
Knüpfer, M.M., Poppenborg, H., Hotfilder, M., Kühnel, K., Wolff, J.E., and Domula, M. (1999). CD44 expression and hyaluronic acid binding of malignant glioma cells. Clin. Exp. Metastasis 17: 71–76, https://doi.org/10.1023/a:1026425519497.10.1023/A:1026425519497Search in Google Scholar PubMed
Kodera, T., Nakagawa, T., Kubota, T., Kabuto, M., Sato, K., and Kobayashi, H. (2000). The expression and activation of matrix metalloproteinase-2 in rat brain after implantation of C6 rat glioma cells. J. Neurooncol. 46: 105–114, https://doi.org/10.1023/a:1006387600909.10.1023/A:1006387600909Search in Google Scholar
Kondo, T., Setoguchi, T., and Taga, T. (2004). Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc. Natl. Acad. Sci. U.S.A. 101: 781–786, https://doi.org/10.1073/pnas.0307618100.Search in Google Scholar PubMed PubMed Central
Lemasson, B., Valable, S., Farion, R., Krainik, A., Rémy, C., and Barbier, E.L. (2013). In vivo imaging of vessel diameter, size, and density: a comparative study between MRI and histology. Magn. Reson. Med. 69: 18–26, https://doi.org/10.1002/mrm.24218.Search in Google Scholar PubMed
Li, J.H., Li, S.Y., Shen, M.X., Qiu, R.Z., Fan, H.W., and Li, Y.B. (2021). Anti-tumor effects of Solanum nigrum L. extraction on C6 high-grade glioma. J. Ethnopharmacol. 274: 114034, https://doi.org/10.1016/j.jep.2021.114034.Search in Google Scholar PubMed
Li, Q., Qiao, G., Ma, J., and Li, Y. (2014). Downregulation of VEGF expression attenuates malignant biological behavior of C6 glioma stem cells. Int. J. Oncol. 44: 1581–1588, https://doi.org/10.3892/ijo.2014.2331.Search in Google Scholar PubMed
Li, S., Li, J., Fan, Y., Huang, T., Zhou, Y., Fan, H., Zhang, Q., and Qiu, R. (2022). The mechanism of formononetin/calycosin compound optimizing the effects of temozolomide on C6 malignant glioma based on metabolomics and network pharmacology. Biomed. Pharmacother 153: 113418, https://doi.org/10.1016/j.biopha.2022.113418.Search in Google Scholar PubMed
Lin, X.-M., Shi, X.-X., Xiong, L., Nie, J.-H., Ye, H.-S., Du, J.-Z., and Liu, J.J.I.J.o.M.S. (2021). Construction of IL-13 receptor α2-targeting resveratrol nanoparticles against glioblastoma cells: therapeutic efficacy and molecular effects. Int. J. Mol. Sci. 22: 10622, https://doi.org/10.3390/ijms221910622.Search in Google Scholar PubMed PubMed Central
Liu, J., Zhou, J., Li, J., Zhang, L., Zhang, P., and Liu, B. (2017). Evaluation of rat C6 malignant glioma using spectral computed tomography. Exp. Ther. Med. 14: 1037–1044, https://doi.org/10.3892/etm.2017.4613.Search in Google Scholar PubMed PubMed Central
Liu, Q., Zhou, L., Lu, R., Yang, C., Wang, S., Hai, L., and Wu, Y. (2021). Biotin and glucose co-modified multi-targeting liposomes for efficient delivery of chemotherapeutics for the treatment of glioma. Bioorg. Med. Chem. 29: 115852, https://doi.org/10.1016/j.bmc.2020.115852.Search in Google Scholar PubMed
Low, J.T., Ostrom, Q.T., Cioffi, G., Neff, C., Waite, K.A., Kruchko, C., and Barnholtz-Sloan, J.S. (2022). Primary brain and other central nervous system tumors in the United States (2014–2018): a summary of the CBTRUS statistical report for clinicians. Neurooncol. Pract. 9: 165–182, https://doi.org/10.1093/nop/npac015.Search in Google Scholar PubMed PubMed Central
Maire, C.L. and Ligon, K.L. (2014). Molecular pathologic diagnosis of epidermal growth factor receptor. Neuro Oncol. 16: viii1–6, https://doi.org/10.1093/neuonc/nou294.Search in Google Scholar PubMed PubMed Central
Manju, C.A., Jeena, K., Ramachandran, R., Manohar, M., Ambily, A.M., Sajesh, K.M., Gowd, G.S., Menon, K., Pavithran, K., Pillai, A., et al.. (2021). Intracranially injectable multi-siRNA nanomedicine for the inhibition of glioma stem cells. Neurooncol. Adv. 3: vdab104, https://doi.org/10.1093/noajnl/vdab104.Search in Google Scholar PubMed PubMed Central
Masuda, J., Takayama, E., Strober, W., Satoh, A., Morimoto, Y., Honjo, Y., Ichinohe, T., Tokuno, S.-I., Ishizuka, T., Nakata, T., et al.. (2017). Tumor growth limited to subcutaneous site vs tumor growth in pulmonary site exhibit differential effects on systemic immunities. Oncol. Rep. 38: 449–455, https://doi.org/10.3892/or.2017.5646.Search in Google Scholar PubMed PubMed Central
Mayas, M.D., Ramírez-Expósito, M.J., Carrera, M.P., Cobo, M., and Martínez-Martos, J.M. (2012). Renin-angiotensin system-regulating aminopeptidases in tumor growth of rat C6 gliomas implanted at the subcutaneous region. Anticancer Res. 32: 3675–3682.Search in Google Scholar
Mayer, J., Kirschstein, T., Resch, T., Porath, K., Krause, B.J., Köhling, R., and Lange, F. (2020). Perampanel attenuates epileptiform phenotype in C6 glioma. Neurosci. Lett. 715: 134629, https://doi.org/10.1016/j.neulet.2019.134629.Search in Google Scholar PubMed
Miura, F.K., Alves, M.J.F., Rocha, M.C., Silva, R.S., Oba-Shinjo, S.M., Uno, M., Colin, C., Sogayar, M.C., and Marie, S.K.J.A.d.n.-p. (2008). Experimental model of C6 brain tumors in athymic rats. Arq. Neuro. Psiquiatr. 66: 238–241, https://doi.org/10.1590/s0004-282x2008000200019.Search in Google Scholar PubMed
Mohammed, S., Dinesan, M., and Ajayakumar, T. (2022). Survival and quality of life analysis in glioblastoma multiforme with adjuvant chemoradiotherapy: a retrospective study. Rep. Pract. Oncol. Radiother 27: 1026–1036, https://doi.org/10.5603/rpor.a2022.0113.Search in Google Scholar
Murgoci, A.N., Cardon, T., Aboulouard, S., Duhamel, M., Fournier, I., Cizkova, D., and Salzet, M. (2020). Reference and ghost proteins identification in rat C6 glioma extracellular vesicles. iScience 23: 101045, https://doi.org/10.1016/j.isci.2020.101045.Search in Google Scholar PubMed PubMed Central
Nagano, N., Sasaki, H., Aoyagi, M., and Hirakawa, K. (1993). Invasion of experimental rat brain tumor: early morphological changes following microinjection of C6 glioma cells. Acta Neuropathol. 86: 117–125, https://doi.org/10.1007/bf00334878.Search in Google Scholar
Oh, T., Fakurnejad, S., Sayegh, E.T., Clark, A.J., Ivan, M.E., Sun, M.Z., Safaee, M., Bloch, O., James, C.D., and Parsa, A.T. (2014). Immunocompetent murine models for the study of glioblastoma immunotherapy. J. Transl. Med. 12: 107, https://doi.org/10.1186/1479-5876-12-107.Search in Google Scholar PubMed PubMed Central
Orozco-Morales, M., Sánchez-García, F.-J., Guevara-Salazar, P., Arrieta, O., Hernández-Pedro, N.Y., Sánchez-García, A., Perez-Madrigal, R., Rangel-López, E., Pineda, B., and Sotelo, J. (2012). Adjuvant immunotherapy of C6 glioma in rats with pertussis toxin. J. Cancer Res. Clin. Oncol. 138: 23–33, https://doi.org/10.1007/s00432-011-1069-y.Search in Google Scholar PubMed
Ostrom, Q.T., Gittleman, H., Truitt, G., Boscia, A., Kruchko, C., and Barnholtz-Sloan, J.S. (2018). CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2011–2015. Neuro Oncol. 20: iv1–iv86, https://doi.org/10.1093/neuonc/noy131.Search in Google Scholar PubMed PubMed Central
Parsa, A.T., Chakrabarti, I., Hurley, P.T., Chi, J.H., Hall, J.S., Kaiser, M.G., and Bruce, J.N. (2000). Limitations of the C6/Wistar rat intracerebral glioma model: implications for evaluating immunotherapy. Neurosurgery 47: 993–999; discussion 999–1000, https://doi.org/10.1097/00006123-200010000-00050.Search in Google Scholar PubMed
Pigula, M., Huang, H.C., Mallidi, S., Anbil, S., Liu, J., Mai, Z., and Hasan, T. (2019). Size-dependent tumor response to photodynamic therapy and irinotecan monotherapies revealed by longitudinal ultrasound monitoring in an orthotopic pancreatic cancer model. Photochem. Photobiol. 95: 378–386, https://doi.org/10.1111/php.13016.Search in Google Scholar PubMed PubMed Central
Pineda, B., Sánchez García, F.J., Olascoaga, N.K., Pérez de la Cruz, V., Salazar, A., Moreno-Jiménez, S., Hernández Pedro, N., Márquez-Navarro, A., Ortiz Plata, A., and Sotelo, J. (2019). Malignant glioma therapy by vaccination with irradiated C6 cell-derived microvesicles promotes an antitumoral immune response. Mol. Ther. 27: 1612–1620, https://doi.org/10.1016/j.ymthe.2019.05.016.Search in Google Scholar PubMed PubMed Central
Plate, K.H., Breier, G., Millauer, B., Ullrich, A., and Risau, W. (1993). Up-regulation of vascular endothelial growth factor and its cognate receptors in a rat glioma model of tumor angiogenesis. Cancer Res. 53: 5822–5827.Search in Google Scholar
Pombo Antunes, A.R., Scheyltjens, I., Duerinck, J., Neyns, B., Movahedi, K., and Van Ginderachter, J.A. (2020). Understanding the glioblastoma immune microenvironment as basis for the development of new immunotherapeutic strategies. eLife 9: 52176, https://doi.org/10.7554/elife.52176.Search in Google Scholar PubMed PubMed Central
Poon, M.T.C., Sudlow, C.L.M., Figueroa, J.D., and Brennan, P.M. (2020). Longer-term (≥ 2 years) survival in patients with glioblastoma in population-based studies pre-and post-2005: a systematic review and meta-analysis. Sci. Rep. 10: 11622, https://doi.org/10.1038/s41598-020-68011-4.Search in Google Scholar PubMed PubMed Central
Pu, P., Liu, X., Liu, A., Cui, J., and Zhang, Y. (2000). Inhibitory effect of antisense epidermal growth factor receptor RNA on the proliferation of rat C6 glioma cells in vitro and in vivo. J. Neurosurg. 92: 132–139, https://doi.org/10.3171/jns.2000.92.1.0132.Search in Google Scholar PubMed
Reyes, S., Herrera, L.A., Ostrosky, P., and Sotelo, J.J.N. (2001). Quinacrine enhances carmustine therapy of experimental rat glioma. Neurosurgery 49: 969–973, https://doi.org/10.1097/00006123-200110000-00033.Search in Google Scholar PubMed
Rivera, E., Arrieta, O., Guevara, P., Duarte-Rojo, A., and Sotelo, J. (2001). AT1 receptor is present in glioma cells; its blockage reduces the growth of rat glioma. Br. J. Cancer 85: 1396–1399, https://doi.org/10.1054/bjoc.2001.2102.Search in Google Scholar PubMed PubMed Central
Sahu, U., Barth, R.F., Otani, Y., McCormack, R., and Kaur, B. (2022). Rat and mouse brain tumor models for experimental neuro-oncology research. J. Neuropathol. Exp. Neurol. 81: 312–329, https://doi.org/10.1093/jnen/nlac021.Search in Google Scholar PubMed PubMed Central
Sajjad, H., Imtiaz, S., Noor, T., Siddiqui, Y.H., Sajjad, A., and Zia, M. (2021). Cancer models in preclinical research: a chronicle review of advancement in effective cancer research. Animal Model Exp. Med. 4: 87–103, https://doi.org/10.1002/ame2.12165.Search in Google Scholar PubMed PubMed Central
Saleh, M., Stacker, S.A., and Wilks, A.F. (1996). Inhibition of growth of C6 glioma cells in vivo by expression of antisense vascular endothelial growth factor sequence. Cancer Res. 56: 393–401.Search in Google Scholar
Samani, A.A., Nalbantoglu, J., and Brodt, P. (2020). Glioma cells with genetically engineered IGF-I receptor downregulation can persist in the brain in a dormant State. Front. Oncol. 10: 555945, https://doi.org/10.3389/fonc.2020.555945.Search in Google Scholar PubMed PubMed Central
Schlegel, J., Piontek, G., Kersting, M., Schuermann, M., Kappler, R., Scherthan, H., Weghorst, C., Buzard, G., and Mennel, H. (1999). The p16/Cdkn2a/Ink4a gene is frequently deleted in nitrosourea-induced rat glial tumors. Pathobiology 67: 202–206, https://doi.org/10.1159/000028073.Search in Google Scholar PubMed
Schmidek, H.H., Nielsen, S.L., Schiller, A.L., and Messer, J. (1971). Morphological studies of rat brain tumors induced by N-nitrosomethylurea. J. Neurosurg. 34: 335–340, https://doi.org/10.3171/jns.1971.34.3.0335.Search in Google Scholar PubMed
Sharifzad, F., Yasavoli-Sharahi, H., Mardpour, S., Fakharian, E., Nikuinejad, H., Heydari, Y., Mardpour, S., Taghikhani, A., Khellat, R., Vafaei, S., et al.. (2019). Neuropathological and genomic characterization of glioblastoma-induced rat model: how similar is it to humans for targeted therapy? J. Cell. Physiol. 234: 22493–22504, https://doi.org/10.1002/jcp.28813.Search in Google Scholar PubMed
Shi, J., Zhang, Y., Fu, W.M., Chen, M., and Qiu, Z. (2015). Establishment of C6 brain glioma models through stereotactic technique for laser interstitial thermotherapy research. Surg. Neurol. Int. 6: 51, https://doi.org/10.4103/2152-7806.154451.Search in Google Scholar PubMed PubMed Central
Sibenaller, Z.A., Etame, A.B., Ali, M.M., Barua, M., Braun, T.A., Casavant, T.L., and Ryken, T.C. (2005). Genetic characterization of commonly used glioma cell lines in the rat animal model system. Neurosurg. Focus 19: E1, https://doi.org/10.3171/foc.2005.19.4.2.Search in Google Scholar PubMed
Singh, D., Dromel, P.C., Perepelkina, T., Baranov, P., and Young, M. (2020). C6 cell injection into the optic nerve of long-evans rats: a short-term model of optic pathway gliomas. Cell Transplant. 29: 963689720964383, https://doi.org/10.1177/0963689720964383.Search in Google Scholar PubMed PubMed Central
Singh, N., Miner, A., Hennis, L., and Mittal, S. (2021). Mechanisms of temozolomide resistance in glioblastoma – a comprehensive review. Cancer Drug Resist. 4: 17–43, https://doi.org/10.20517/cdr.2020.79.Search in Google Scholar PubMed PubMed Central
Slavkova, K.P., Patel, S.H., Cacini, Z., Kazerouni, A.S., Gardner, A.L., Yankeelov, T.E., and Hormuth, D.A. (2023). Mathematical modelling of the dynamics of image-informed tumor habitats in a murine model of glioma. Sci. Rep. 13: 2916, https://doi.org/10.1038/s41598-023-30010-6.Search in Google Scholar PubMed PubMed Central
Song, T.-W., Lee, J.-K., Lee, S.-Y., Lian, S., Joo, S.-P., and Kim, H.-S.J.T.N. (2016). Establishment of a malignant glioma model in rats. The Nerve 2: 17–21, https://doi.org/10.21129/nerve.2016.2.2.17.Search in Google Scholar
Stribbling, S.M. and Ryan, A.J. (2022). The cell-line-derived subcutaneous tumor model in preclinical cancer research. Nat. Protoc. 17: 2108–2128, https://doi.org/10.1038/s41596-022-00709-3.Search in Google Scholar PubMed
Taheri, B., Soleimani, M., Aval, S.F., Memari, F., and Zarghami, N. (2018). C6 glioma-derived microvesicles stimulate the proliferative and metastatic gene expression of normal astrocytes. Neurosci. Lett. 685: 173–178, https://doi.org/10.1016/j.neulet.2018.08.034.Search in Google Scholar PubMed
Tan, X., Kim, G., Lee, D., Oh, J., Kim, M., Piao, C., Lee, J., Lee, M.S., Jeong, J.H., and Lee, M. (2018). A curcumin-loaded polymeric micelle as a carrier of a microRNA-21 antisense-oligonucleotide for enhanced anti-tumor effects in a glioblastoma animal model. Biomater. Sci. 6: 407–417, https://doi.org/10.1039/c7bm01088e.Search in Google Scholar PubMed
Tankov, S. and Walker, P.R. (2021). Glioma-derived extracellular vesicles – far more than local mediators. Front. Immunol. 12: 679954, https://doi.org/10.3389/fimmu.2021.679954.Search in Google Scholar PubMed PubMed Central
Tao, J., Fei, W., Tang, H., Li, C., Mu, C., Zheng, H., Li, F., and Zhu, Z. (2019). Angiopep-2-conjugated “Core-Shell” hybrid nanovehicles for targeted and pH-triggered delivery of arsenic trioxide into glioma. Mol. Pharm. 16: 786–797, https://doi.org/10.1021/acs.molpharmaceut.8b01056.Search in Google Scholar PubMed
Taylor, M.A., Hughes, A.M., Walton, J., Coenen-Stass, A.M.L., Magiera, L., Mooney, L., Bell, S., Staniszewska, A.D., Sandin, L.C., Barry, S.T., et al.. (2019). Longitudinal immune characterization of syngeneic tumor models to enable model selection for immune oncology drug discovery. J. Immunother Cancer 7: 328, https://doi.org/10.1186/s40425-019-0794-7.Search in Google Scholar PubMed PubMed Central
Trejo-Solís, C., Palencia, G., Zuñiga, S., Rodríguez-Ropon, A., Osorio-Rico, L., Torres Luvia, S., Gracia-Mora, I., Marquez-Rosado, L., Sánchez, A., Moreno-García, M.E., et al.. (2005). Cas ilgly induces apoptosis in glioma C6 cells in vitro and in vivo through caspase-dependent and caspase-independent mechanisms. Neoplasia 7: 563–574, https://doi.org/10.1593/neo.04607.Search in Google Scholar PubMed PubMed Central
Turna, A., Kıran, B., Ozar, E., Turna, H., Mercan, C.A., Büyükpınarbaşılı, N., Bilir, A., and Deniz, G.J.T.J.o.I. (2013). Interleukin-12 and protamine inhibit angiogenesis and growth of C6 rat glioma: synergistic effects and role of Th2 cells. Turk. J. Immunol. 1: 68–73, https://doi.org/10.5606/tji.2013.268.Search in Google Scholar
Tzerkovsky, D.A., Osharin, V.V., Istomin, Y.P., Alexandrova, E.N., and Vozmitel, M.A. (2014). Fluorescent diagnosis and photodynamic therapy for C6 glioma in combination with antiangiogenic therapy in subcutaneous and intracranial tumor models. Exp. Oncol. 36: 85–89.Search in Google Scholar
Varna, M., Bertheau, P., and Legrès, L.G.J.J.o.A.O. (2014). Tumor microenvironment in human tumor xenografted mouse models. J. Anal. Oncol. 3: 159–166.10.6000/1927-7229.2014.03.03.6Search in Google Scholar
Vinores, S.A. and Koestner, A. (1981). Effect of nerve growth factor producing cells on anaplastic glioma and pheochromocytoma clones: involvement of other factors. J. Neurosci. Res. 6: 389–401, https://doi.org/10.1002/jnr.490060314.Search in Google Scholar PubMed
Wang, D., Lu, Y., Li, X., Mei, N., Wu, P.Y., Geng, D., Wu, H., and Yin, B. (2022). Evaluation of HIF-1α expression in a rat glioma model using intravoxel incoherent motion and R2* mapping. Front. Oncol. 12: 902612, https://doi.org/10.3389/fonc.2022.902612.Search in Google Scholar PubMed PubMed Central
Watabe, T., Ikeda, H., Nagamori, S., Wiriyasermkul, P., Tanaka, Y., Naka, S., Kanai, Y., Hagiwara, K., Aoki, M., Shimosegawa, E., et al.. (2017). (18)F-FBPA as a tumor-specific probe of L-type amino acid transporter 1 (LAT1): a comparison study with (18)F-FDG and (11)C-Methionine PET. Eur. J. Nucl. Med. Mol. Imaging 44: 321–331, https://doi.org/10.1007/s00259-016-3487-1.Search in Google Scholar PubMed
Watanabe, K., Sakamoto, M., Somiya, M., Amin, M.R., Kamitani, H., and Watanabe, T. (2002). Feasibility and limitations of the rat model by C6 gliomas implanted at the subcutaneous region. Neurol. Res. 24: 485–490, https://doi.org/10.1179/016164102101200221.Search in Google Scholar PubMed
Woroniecka, K., Chongsathidkiet, P., Rhodin, K., Kemeny, H., Dechant, C., Farber, S.H., Elsamadicy, A.A., Cui, X., Koyama, S., Jackson, C., et al.. (2018). T-cell exhaustion signatures vary with tumor type and are severe in glioblastoma. Clin. Cancer Res. 24: 4175–4186, https://doi.org/10.1158/1078-0432.ccr-17-1846.Search in Google Scholar PubMed PubMed Central
Wu, H., Wang, C., Liu, J., Zhou, D., Chen, D., Liu, Z., Wu, A., Yang, L., Chang, J., Luo, C., et al.. (2020). Evaluation of a tumor electric field treatment system in a rat model of glioma. CNS Neurosci. Ther. 26: 1168–1177, https://doi.org/10.1111/cns.13441.Search in Google Scholar PubMed PubMed Central
Wu, L., Li, Q., Deng, J., Shen, J., Xu, W., Yang, W., Chen, B., Du, Y., Zhang, W., Ge, F.J.I.J.o. N., et al.. (2021). Platelet-tumor cell hybrid membrane-camouflaged nanoparticles for enhancing therapy efficacy in glioma. Int. J. Nanomedicine 16: 8433, https://doi.org/10.2147/ijn.s333279.Search in Google Scholar
Wu, S.K., Santos, M.A., Marcus, S.L., and Hynynen, K. (2019). MR-guided focused ultrasound facilitates sonodynamic therapy with 5-aminolevulinic acid in a rat glioma model. Sci. Rep. 9: 10465, https://doi.org/10.1038/s41598-019-46832-2.Search in Google Scholar PubMed PubMed Central
Xiong, J., Zhou, L., Lim, Y., Yang, M., Zhu, Y.-H., Li, Z.-W., Zhou, F.H., Xiao, Z.-C., and Zhou, X.-F. (2013). Mature BDNF promotes the growth of glioma cells in vitro. Oncol. Rep. 30: 2719–2724, https://doi.org/10.3892/or.2013.2746.Search in Google Scholar PubMed
Xu, C.S., Wang, Z.F., Dai, L.M., Chu, S.H., Gong, L.L., Yang, M.H., and Li, Z.Q. (2014). Induction of proline-rich tyrosine kinase 2 activation-mediated C6 glioma cell invasion after anti-vascular endothelial growth factor therapy. J. Transl. Med. 12: 148, https://doi.org/10.1186/1479-5876-12-148.Search in Google Scholar PubMed PubMed Central
Xu, Y., Yang, X., Mei, S., Sun, Y., and Li, J. (2019). Acquisition of temozolomide resistance by the rat C6 glioma cell line increases cell migration and side population phenotype. Oncol. Rep. 42: 2355–2362, https://doi.org/10.3892/or.2019.7350.Search in Google Scholar PubMed PubMed Central
Yan, G., Yi, M., Li, S., Yang, L., Dai, Z., Xuan, Y., and Wu, R. (2021). Quantitative metabolic characteristics in the peritumoral region of gliomas at 7T. Technol. Health Care 29: 509–517, https://doi.org/10.3233/thc-218048.Search in Google Scholar
Yang, C., Xia, Z., Li, T., Chen, Y., Zhao, M., Sun, Y., Ma, J., Wu, Y., Wang, X., Wang, P., et al.. (2020a). Antioxidant effect of propofol in gliomas and its association with divalent metal transporter 1. Front. Oncol. 10: 590931, https://doi.org/10.3389/fonc.2020.590931.Search in Google Scholar PubMed PubMed Central
Yang, H., Chen, W., Ma, J., Zhao, J., Li, D., Cao, Y., and Liu, P. (2020b). Silver nanotriangles and chemotherapeutics synergistically induce apoptosis in glioma cells via a ROS-dependent mitochondrial pathway. Int. J. Nanomed. 15: 7791–7803, https://doi.org/10.2147/ijn.s267120.Search in Google Scholar PubMed PubMed Central
Yang, L., Lin, Z., Huang, Q., Lin, J., Chen, Z., Zhou, L., and Zhang, P. (2011). Effect of vascular endothelial growth factor on remodeling of C6 glioma tissue in vivo. J. Neurooncol. 103: 33–41, https://doi.org/10.1007/s11060-010-0356-9.Search in Google Scholar PubMed
Yang, W.-H., Cheng, C.-Y., Chen, M.-F., and Wang, T.-C.J.A.R. (2018). Cell subpopulations overexpressing p75NTR have tumor-initiating properties in the C6 glioma cell line. Anticancer Res. 38: 5183–5192, https://doi.org/10.21873/anticanres.12841.Search in Google Scholar PubMed
Yao, N.-W., Chang, C., Lin, H.-T., Yen, C.-T., and Chen, J.-Y.J.S.R. (2016). Functional assessment of glioma pathogenesis by in vivo multi-parametric magnetic resonance imaging and in vitro analyses. Sci. Rep. 6: 1–12, https://doi.org/10.1038/srep26050.Search in Google Scholar PubMed PubMed Central
Yao, Q., Cai, G., Yu, Q., Shen, J., Gu, Z., Chen, J., Shi, W., and Shi, J. (2018). IDH1 mutation diminishes aggressive phenotype in glioma stem cells. Int. J. Oncol. 52: 270–278, https://doi.org/10.3892/ijo.2017.4186.Search in Google Scholar PubMed
Yi, N., Oh, B., Kim, H.A., and Lee, M. (2014). Combined delivery of BCNU and VEGF siRNA using amphiphilic peptides for glioblastoma. J. Drug Target. 22: 156–164, https://doi.org/10.3109/1061186x.2013.850502.Search in Google Scholar PubMed
Yin, W., Zhang, K., Deng, Q., Yu, Q., Mao, Y., Zhao, R., and Ma, S. (2021). AZD3759 inhibits glioma through the blockade of the epidermal growth factor receptor and Janus kinase pathways. Bioengineered 12: 8679–8689, https://doi.org/10.1080/21655979.2021.1991160.Search in Google Scholar PubMed PubMed Central
Zhou, X., Wang, X., Qu, F., Zhong, Y., Lu, X., Zhao, P., Wang, D., Huang, Q., Zhang, L., and Li, X.J.J.o. I.M.R. (2009). Detection of cancer stem cells from the C6 glioma cell line. J Int Med Res 37: 503–510, https://doi.org/10.1177/147323000903700226.Search in Google Scholar PubMed
Zhu, J., Zhang, Y., Chen, X., Zhang, Y., Zhang, K., Zheng, H., Wei, Y., Zheng, H., Zhu, J., Wu, F., et al.. (2021). Angiopep-2 modified lipid-coated mesoporous silica nanoparticles for glioma targeting therapy overcoming BBB. Biochem. Biophys. Res. Commun. 534: 902–907, https://doi.org/10.1016/j.bbrc.2020.10.076.Search in Google Scholar PubMed
© 2023 Walter de Gruyter GmbH, Berlin/Boston