biostudies-literatureMancarella SMinistero della SaluteFondazione AIRC per la ricerca sul cancro ETS286https://www.ebi.ac.uk/biostudies/studies/S-EPMC11484308biostudies-literatureUnknown43(1)<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>hCAFs/iCCA cross-talk sustains increased migration of both KKU-M213 and KKU-M156 cells, whiJournal of experimental & clinical cancer research : CRTargeting cancer-associated fibroblasts/tumor cells cross-talk inhibits intrahepatic cholangiocarcinoma progression via cell-cycle arrest.PMC11484308Ricerca Corrente 2024IG 2020 ID 24815Pizzuto EDe Bellis MArdito FTerzi ADituri FVincenti LMaiorano EMancarella SSerino GCalvisi DFGiannelli GGigante IfalseTargeting cancer-associated fibroblasts/tumor cells cross-talk inhibits intrahepatic cholangiocarcinoma progression via cell-cycle arrest.<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>hCAFs/iCCA cross-talk sustains increased migration of both KKU-M213 and KKU-M156 cells, whi2024-01-01T00:00:00Z2024 Oct2026-04-30T00:05:56.247Z2025-04-06T14:23:23.378ZS-EPMC114843083941528610.1186/s13046-024-03210-9