Affo, Silvia and Nair, Ajay and Brundu, Francesco and Ravichandra, Aashreya and Bhattacharjee, Sonakshi and Matsuda, Michitaka and Chin, LiKang and Filliol, Aveline and Wen, Wen and Song, Xinhua and Decker, Aubrianna and Worley, Jeremy and Caviglia, Jorge Matias and Yu, Lexing and Yin, Deqi and Saito, Yoshinobu and Savage, Thomas and Wells, Rebecca G. and Mack, Matthias and Zender, Lars and Arpaia, Nicholas and Remotti, Helen E. and Rabadan, Raul and Sims, Peter and Leblond, Anne-Laure and Weber, Achim and Riener, Marc-Oliver and Stockwell, Brent R. and Gaublomme, Jellert and Llovet, Josep M. and Kalluri, Raghu and Michalopoulos, George K. and Seki, Ekihiro and Sia, Daniela and Chen, Xin and Califano, Andrea and Schwabe, Robert F. (2021) Promotion of cholangiocarcinoma growth by diverse cancer-associated fibroblast subpopulations. CANCER CELL, 39 (6). 866-+. ISSN 1535-6108, 1878-3686
Full text not available from this repository. (Request a copy)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 themain source of CAF and HSC-derived CAF as the dominant population interacting with tumor cells. In mice, CAF promotes ICC progression, as revealed by HSC-selective CAF depletion. In patients, a high pan-CAF signature is associated with decreased survival and increased recurrence. Single-cell RNA sequencing segregates CAF into inflammatory and growth factor-enriched (iCAF) and myofibroblastic (myCAF) subpopulations, displaying distinct ligand-receptor interactions. myCAF-expressed hyaluronan synthase 2, but not type I collagen, promotes ICC. iCAF-expressed hepatocyte growth factor enhances ICC growth via tumor-expressed MET, thus directly linking CAF to tumor cells. In summary, our data demonstrate promotion of desmoplastic ICC growth by therapeutically targetable CAF subtype-specific mediators, but not by type I collagen.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HEPATIC STELLATE CELLS; LIVER FIBROSIS; HYALURONAN; REVEALS; CHEMORESISTANCE; CONTRIBUTE; FORCE; GENE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 04 Oct 2022 07:21 |
| Last Modified: | 04 Oct 2022 07:21 |
| URI: | https://pred.uni-regensburg.de/id/eprint/48189 |
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