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Promotion of cholangiocarcinoma growth by diverse cancer-associated fibroblast subpopulations

Authors: Affo, Silvia; Nair, Ajay; Brundu, Francesco; Ravichandra, Aashreya; Bhattacharjee, Sonakshi; Matsuda, Michitaka; Chin, LiKang; Filliol, Aveline; Wen, Wen; Song, Xinhua; Decker, Aubrianna; Worley, Jeremy; Caviglia, Jorge Matias; Yu, Lexing; Yin, Deqi; Saito, Yoshinobu; Savage, Thomas; Wells, Rebecca G.; Mack, Matthias; Zender, Lars; Arpaia, Nicholas; Remotti, Helen E.; Rabadan, Raul; Sims, Peter; Leblond, Anne-Laure; Weber, Achim; Riener, Marc-Oliver; Stockwell, Brent R.; Gaublomme, Jellert; Llovet, Josep M.; Michalopoulos, George K.; Seki, Ekihiro; Sia, Daniela; Chen, Xin; Califano, Andrea; Schwabe, Robert F.

Online: https://www.sciencedirect.com/science/article/pii/S1535610821001707

Issue: Cancer Cell. 2021 Jun 14;39(6):866-882.e11.

Abstract

Cancer-associated fibroblasts (CAF) are a poorly characterized cell population in the context of liver cancer. Our study investigates CAF functions in intrahepatic cholangiocarcinoma (ICC), a highly desmoplastic liver tumor. Genetic tracing, single-cell RNA sequencing, and ligand-receptor analyses uncovered hepatic stellate cells (HSC) as the main source of CAF and HSC-derived CAF as the dominant population interacting with tumor cells. In mice, CAF promotes ICC progression, as