Targeting cancer-associated fibroblasts/tumor cells cross-talk inhibits intrahepatic cholangiocarcinoma progression via cell-cycle arrest.

ABSTRACT:

Background

Cancer-associated fibroblasts (CAFs), mainly responsible for the desmoplastic reaction hallmark of intrahepatic Cholangiocarcinoma (iCCA), likely have a role in tumor aggressiveness and resistance to therapy, although the molecular mechanisms involved are unknown. Aim of the study is to investigate how targeting hCAF/iCCA cross-talk with a Notch1 inhibitor, namely Crenigacestat, may affect cancer progression.

Methods

We used different in vitro models in 2D and established new 3D hetero-spheroids with iCCA cells and human (h)CAFs. The results were confirmed in a xenograft model, and explanted tumoral tissues underwent transcriptomic and bioinformatic analysis.

Results

hCAFs/iCCA cross-talk sustains increased migration of both KKU-M213 and KKU-M156 cells, whi

SUBMITTER: Mancarella S 

PROVIDER: S-EPMC11484308 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature