αSMA⁺ fibroblasts suppress Lgr5⁺ cancer stem cells and restrain colorectal cancer progression.

ABSTRACT: 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⁺ regulator

SUBMITTER: McAndrews KM 

PROVIDER: S-EPMC9150816 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature