RRC ID 73378
Author Rattanasinchai C, Navasumrit P, Ruchirawat M.
Title Elevated ITGA2 expression promotes collagen type I-induced clonogenic growth of intrahepatic cholangiocarcinoma.
Journal Sci Rep
Abstract Intrahepatic cholangiocarcinoma (iCCA) arises along the peripheral bile ducts and is often accompanied by a tumor microenvironment (TME) high in extracellular matrices (ECMs). In this study, we aimed to evaluate whether an ECM-rich TME favors iCCA progression. We identified ITGA2, which encodes collagen-binding integrin α2, to be differentially-expressed in iCCA tumors compared with adjacent normal tissues. Elevated ITGA2 is also positively-correlated with its ligand, collagen type I. Increased ITGA2 expression and its role in collagen type I binding was validated in vitro using four iCCA cell lines, compared with a non-cancerous, cholangiocyte cell line. Robust interaction of iCCA cells with collagen type I was abolished by either ITGA2 depletion or integrin α2β1-selective inhibitor treatment. In a phenotypic study, collagen type I significantly enhances clonogenic growth of HuCCA-1 and HuCCT-1 cells by three and sixfold, respectively. Inhibition of integrin α2 expression or its activity significantly blocks collagen type I-induced colony growth in both cell lines. Taken together, our data provide mechanistic evidence that collagen type I promotes growth of iCCA colonies through integrin α2 suggesting that the collagen type I-integrin α2 axis could be a promising target for cancer prevention and a therapeutic opportunity for this cancer.
Volume 12(1)
Pages 22429
Published 2022-12-27
DOI 10.1038/s41598-022-26747-1
PII 10.1038/s41598-022-26747-1
PMID 36575207
PMC PMC9794692
MeSH Bile Duct Neoplasms* / genetics Bile Duct Neoplasms* / pathology Bile Ducts, Intrahepatic / pathology Cholangiocarcinoma* / genetics Cholangiocarcinoma* / pathology Collagen Type I / genetics Humans Integrin alpha2 / genetics Tumor Microenvironment
IF 3.998
Human and Animal Cells HuCCT1(RCB1960)