THBS1 and THBS2 Enhance the In Vitro Proliferation, Adhesion, Migration and Invasion of Intrahepatic Cholangiocarcinoma Cells
-
Published:2024-02-01
Issue:3
Volume:25
Page:1782
-
ISSN:1422-0067
-
Container-title:International Journal of Molecular Sciences
-
language:en
-
Short-container-title:IJMS
Author:
Corbella Eleonora1, Fara Claudia1, Covarelli Francesca1, Porreca Veronica1, Palmisano Biagio2ORCID, Mignogna Giuseppina3ORCID, Corsi Alessandro1ORCID, Riminucci Mara1ORCID, Maras Bruno3ORCID, Mancone Carmine1ORCID
Affiliation:
1. Department of Molecular Medicine, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy 2. Department of Radiology, Oncology and Pathology, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy 3. Department of Biochemistry Science, Sapienza University of Rome, Viale Regina Elena 332, 00185 Rome, Italy
Abstract
In intrahepatic cholangiocarcinoma (iCCA), thrombospondin 1 (THBS1) and 2 (THBS2) are soluble mediators released in the tumor microenvironment (TME) that contribute to the metastatic spreading of iCCA cells via a lymphatic network by the trans-differentiation of vascular endothelial cells to a lymphatic-like phenotype. To study the direct role of THBS1 and THBS2 on the iCCA cells, well-established epithelial (HuCCT-1) and mesenchymal (CCLP1) iCCA cell lines were subjected to recombinant human THBS1 and THBS2 (rhTHBS1, rhTHBS2) for cellular function assays. Cell growth, cell adhesion, migration, and invasion were all enhanced in both CCLP1 and HuCCT-1 cells by the treatment with either rhTHBS1 or rhTHBS2, although they showed some variability in their intensity of speeding up cellular processes. rhTHBS2 was more intense in inducing invasiveness and in committing the HuCCT-1 cells to a mesenchymal-like phenotype and was therefore a stronger enhancer of the malignant behavior of iCCA cells compared to rhTHBS1. Our data extend the role of THBS1 and THBS2, which are not only able to hinder the vascular network and promote tumor-associated lymphangiogenesis but also exacerbate the malignant behavior of the iCCA cells.
Funder
AMMF—The Cholangiocarcinoma Charity the Next Generation EU—Italian Ministry of University and Research (MUR) PRIN 2022 Sapienza University of Rome—Fondi di Ateneo
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference42 articles.
1. Cholangiocarcinoma 2020: The next horizon in mechanisms and management;Banales;Nat. Rev. Gastroenterol. Hepatol.,2020 2. Molecular Mechanisms Driving Cholangiocarcinoma Invasiveness: An Overview;Brivio;Gene Expr.,2018 3. Cadamuro, M., Romanzi, A., Guido, M., Sarcognato, S., Cillo, U., Gringeri, E., Zanus, G., Strazzabosco, M., Simioni, P., and Villa, E. (2022). Translational Value of Tumor-Associated Lymphangiogenesis in Cholangiocarcinoma. J. Pers. Med., 12. 4. Tumor reactive stroma in cholangiocarcinoma: The fuel behind cancer aggressiveness;Brivio;World J. Hepatol.,2017 5. Matrisome analysis of intrahepatic cholangiocarcinoma unveils a peculiar cancer-associated extracellular matrix structure;Carpino;Clin. Proteomics,2019
|
|