小柯机器人

美国哥伦比亚大学Robert F. Schwabe研究小组发现，不同的癌症相关成纤维细胞亚群促进胆管癌的生长。2021年4月29日，国际知名学术期刊《癌细胞》在线发表了这一成果。

研究人员调查了癌症相关成纤维细胞（CAF）在肝内胆管癌（ICC）中的作用，这是一种高度促结缔织增生的肝肿瘤。遗传示踪、单细胞RNA测序和配体-受体分析发现，肝星状细胞（HSC）是CAF的主要来源，而HSC衍生的CAF是与肿瘤细胞相互作用的主要群体。在小鼠中，研究人员通过HSC选择性CAF敲除发现，CAF促进ICC进程。

在患者中，高水平的泛CAF特征与存活率降低和复发增加相关。单细胞RNA测序将CAF区分为炎性和生长因子富集（iCAF）和肌成纤维细胞（myCAF）亚群，并显示出独特的配体-受体相互作用。myCAF表达的透明质酸合酶2而非I型胶原可促进ICC。iCAF表达的肝细胞生长因子通过肿瘤表达的MET增强ICC的生长，从而将CAF直接连接到肿瘤细胞。

总之，这些数据表明可治疗靶向的CAF亚型特异性介导者促进了增生性ICC的生长，而不是通过I型胶原蛋白。

据悉，在肝癌的背景下，CAF是特征不明确的细胞群。

附：英文原文

Title: Promotion of cholangiocarcinoma growth by diverse cancer-associated fibroblast subpopulations

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

Issue&Volume: 2021-04-29

Abstract: Cancer-associated fibroblasts (CAF) are a poorly characterized cell population inthe context of liver cancer. Our study investigates CAF functions in intrahepaticcholangiocarcinoma (ICC), a highly desmoplastic liver tumor. Genetic tracing, single-cellRNA sequencing, and ligand-receptor analyses uncovered hepatic stellate cells (HSC)as the main source of CAF and HSC-derived CAF as the dominant population interactingwith tumor cells. In mice, CAF promotes ICC progression, as revealed by HSC-selectiveCAF depletion. In patients, a high panCAF signature is associated with decreased survivaland increased recurrence. Single-cell RNA sequencing segregates CAF into inflammatoryand growth factor-enriched (iCAF) and myofibroblastic (myCAF) subpopulations, displayingdistinct ligand-receptor interactions. myCAF-expressed hyaluronan synthase 2, butnot type I collagen, promotes ICC. iCAF-expressed hepatocyte growth factor enhancesICC growth via tumor-expressed MET, thus directly linking CAF to tumor cells. In summary,our data demonstrate promotion of desmoplastic ICC growth by therapeutically targetableCAF subtype-specific mediators, but not by type I collagen.

DOI: 10.1016/j.ccell.2021.03.012

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(21)00170-7

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
官方网址：https://www.cell.com/cancer-cell/home
投稿链接：https://www.editorialmanager.com/cancer-cell/default.aspx