Abstract
AbstractClear cell Renal Cell Carcinoma (ccRCC) is one of the most prevalent kidney cancers, which is often asymptomatic and thus discovered at a metastatic state (mRCC). mRCC are highly heterogeneous tumors composed of subclonal populations that lead to poor treatment response rate. Several recent works explored the potential of ccRCC tumoroids culture derived from patients. However, these models were produced following a scaffold-based method using collagen I or Matrigel that exhibit lot variability and whose complexity could induce treatment response modifications and phenotypic alterations. Following the observation that ccRCC tumoroids can create their own niche by secreting extracellular matrix components, we developed the first scaffold-free tumoroid model of ccRCC tumors. Tumoroids from mice as well as from human tumors were generated with high success rate (≥90%) using a magnetic suspension method and standard culture media. Immunofluorescence analysis revealed their self-organization capacities to maintain multiple tumor-resident cell types, including endothelial progenitor cells. Transcriptomic analysis showed the reproducibility of the method highlighting that the majority of gene expression patterns was conserved in tumoroids compared to their matching tumor tissue. Moreover, this model enables to evaluate drug effects and invasiveness of renal cancer cells in a 3D context, providing a robust preclinical tool for drug screening and biomarker assessment in line with alternative ex vivo methods like tumor tissue slice culture or in vivo xenograft models.
Funder
EC | Horizon 2020 Framework Programme
INSERM, CEA, Ligue Comité de l’Isère, University Grenoble Alpes, Centre Hospitalier Universitaire de Grenoble-Alpes (CHUGA), Groupement des Entreprises Françaises dans la Lutte contre le Cancer
CEA, UGA
CEA, Inserm
UGA, Inserm, CEA
CHU, Ligue Comité de l’Isère
Inserm, Ligue Comité de l’Isère
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Cell Biology,Cellular and Molecular Neuroscience,Immunology
Reference61 articles.
1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.
2. Wallis CJD. Epidemiology and etiology of kidney cancer. Urotoday. 2018;1–5. https://www.urotoday.com/library-resources/kidney-cancer-today/109190-epidemiology-and-etiology-of-kidney-cancer.html#.
3. Warren AY, Harrison D. WHO/ISUP classification, grading and pathological staging of renal cell carcinoma: standards and controversies. World J Urol. 2018;36:1913–26.
4. Galsky MD. Metastatic renal cancer: better never than late. Eur Urol. 2014;65:1093–4.
5. Escudier B, Porta C, Schmidinger M, Algaba F, Patard JJ, Khoo V, et al. Renal cell carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25:iii49–56.