Spatiotemporal regulation of cholangiocarcinoma growth and dissemination by peritumoral myofibroblasts in a Vcam1-dependent manner.

ABSTRACT: Intrahepatic cholangiocarcinoma (iCCA) is characterized by its highly desmoplastic stroma. Myofibroblasts (MFs) are present both within the tumor mass (intratumoral MFs, iMFs) and at the tumor border (peritumoral MFs, pMFs). Using a spheroid-based coculture system, we show that the initial iCCA-pMF contact is growth suppressive to the tumor cells. However, prolonged iCCA-pMF interaction elicits significant tumor cell invasion and dissemination. We find that vascular cell adhesion molecule-1 (Vcam1) level is elevated in tumor cells in contact with pMFs but low in disseminated tumor cells both in vitro and in vivo. A gene regulatory network analysis of mouse and patient iCCA tumors and Vcam1 knockout (Vcam1^KO) demonstrate a heavy involvement of Vcam1 in epithelial-to-mesenchymal t

SUBMITTER: Tian C 

PROVIDER: S-EPMC10079548 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature