αSMA+ fibroblasts suppress differentiation of Lgr5+ cancer stem cells via BMP4 and restrain progression of colorectal cancer

Purpose: This study interrogated the role of αSMA+ CAFs in a genetic moue model of metastatic colorectal cancer. Methods: αSMA+ CAFs were selectively depleted in mouse CRC model. RNA was isolated from tumors from control and depleted mice, as well as from the colon of WT mice and sequenced. Results: Mice with αSMA+ CAF-depletion exhibited increased inflammation and immunosuppressive phenotype in tumors. Depleted mice also had an increased incidence of Lgr5+ CSCs. BMP4 and TGFβ1 was increased in depleted tumors compared to control. Conclusion: αSMA+ CAFs have a tumor restraining function in CRC, via BMP4/TGFβ1 signaling. Total RNA sequenced from tumors from 3 control and 3 depleted mice, as well as normal colon epithelium from 3 WT mice.