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

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 alpha SMA(+) CAFs in a genetic mouse model of metastatic colorectal cancer (CRC). Selective depletion of alpha SMA(+) CAFs resulted in increased tumor invasiveness, lymph node metastasis, and reduced overall survival. Depletion of alpha SMA(+) CAFs reduced BMP4 and increased TGF beta 1 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 alpha SMA(+) CAFs in CRC exert tumor-restraining functions via BMP4/TGF beta 1 paracrine signaling that serves to suppress Lgr5(+) CSCs and promote anti-tumor immunity, ultimately limiting CRC progression.

Automated summary

The study demonstrates that alpha SMA(+) CAFs in CRC exert tumor-restraining functions via BMP4/TGF beta 1 paracrine signaling that serves to suppress Lgr5(+) CSCs and promote anti-tumor immunity, ultimately limiting CRC progression.