生物
癌症研究
胰腺癌
上皮-间质转换
间充质干细胞
肿瘤微环境
癌症
表型
细胞生物学
癌变
胰腺
作者
Erin Helms,Mark W. Berry,R. Crystal Chaw,Christopher C. DuFort,Duanchen Sun,M. Kathrina Onate,Chet Oon,Sohinee Bhattacharyya,Hannah Sanford-Crane,Wesley Horton,Jennifer M. Finan,Ariana Sattler,Rosemary Makar,David W. Dawson,Zheng Xia,Sunil R. Hingorani,Mara H. Sherman
出处
期刊:Cancer Discovery
[American Association for Cancer Research]
日期:2021-09-21
被引量:3
标识
DOI:10.1158/2159-8290.cd-21-0601
摘要
Cancer-associated fibroblast (CAF) heterogeneity is increasingly appreciated, but the origins and functions of distinct CAF subtypes remain poorly understood. The abundant and transcriptionally diverse CAF population in pancreatic ductal adenocarcinoma (PDAC) is thought to arise from a common cell of origin, pancreatic stellate cells (PSCs), with diversification resulting from cytokine and growth factor gradients within the tumor microenvironment. Here we analyzed the differentiation and function of PSCs during tumor progression in vivo. Contrary to expectations, we found that PSCs give rise to a numerically minor subset of PDAC CAFs. Targeted ablation of PSC-derived CAFs within their host tissue revealed non-redundant functions for this defined CAF population in shaping the PDAC microenvironment, including production of specific extracellular matrix components and tissue stiffness regulation. Together, these findings link stromal evolution from distinct cells of origin to transcriptional heterogeneity among PDAC CAFs, and demonstrate unique functions for CAFs of a defined cellular origin.
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