LGR5型
癌相关成纤维细胞
肿瘤微环境
生物
癌症干细胞
结直肠癌
癌症研究
干细胞
肿瘤进展
间质细胞
旁分泌信号
癌症
癌细胞
转移
免疫学
细胞生物学
肿瘤细胞
受体
生物化学
遗传学
作者
Kathleen M. McAndrews,Karina Vázquez-Arreguín,Changsoo Kwak,Hikaru Sugimoto,Xiaofeng Zheng,Bingrui Li,Michelle L. Kirtley,Valerie S. LeBleu,Raghu Kalluri
出处
期刊:Oncogene
[Springer Nature]
日期:2021-06-09
卷期号:40 (26): 4440-4452
被引量:23
标识
DOI:10.1038/s41388-021-01866-7
摘要
The development and progression of solid tumors is dependent on cancer cell autonomous drivers and the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) in the TME possess both tumor-promoting and tumor-restraining functions. In the current study, we interrogated the role of αSMA+ CAFs in a genetic mouse model of metastatic colorectal cancer (CRC). Selective depletion of αSMA+ CAFs resulted in increased tumor invasiveness, lymph node metastasis, and reduced overall survival. Depletion of αSMA+ CAFs reduced BMP4 and increased TGFβ1 secretion from stromal cells, and was associated with increased Lgr5+ cancer stem-like cells (CSCs) and the generation of an immunosuppressive TME with increased frequency of Foxp3+ regulatory T cells and suppression of CD8+ T cells. This study demonstrates that αSMA+ CAFs in CRC exert tumor-restraining functions via BMP4/TGFβ1 paracrine signaling that serves to suppress Lgr5+ CSCs and promote anti-tumor immunity, ultimately limiting CRC progression.
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