Fibroblastic FAP promotes intrahepatic cholangiocarcinoma growth via MDSCs recruitment.

Fibroblastic FAP promotes intrahepatic cholangiocarcinoma growth via MDSCs recruitment. Neoplasia. 2019 Nov 20;21(12):1133-1142 Authors: Lin Y, Li B, Yang X, Cai Q, Liu W, Tian M, Luo H, Yin W, Song Y, Shi Y, He R Abstract Desmoplasia is a hallmark of intrahepatic cholangiocarcinoma (ICC), which constitutes a barrier to infiltration of lymphocyte, but not myeloid cells. Given that dense desmoplastic stroma has been reported to be a barrier to infiltration of lymphocyte, but not myeloid cells. We here investigated whether fibroblastic FAP influenced ICC progression via non-T cell-related immune mechanisms. We demonstrated fibroblastic FAP expression was critical for STAT3 activation and CCL2 production, and ICC-CAFs were the primary source of CCL2 in human ICC microenvironment by using ICC-Fbs from six ICC patients. Fibroblastic knockdown of FAP significantly impaired the ability of ICC-CAFs to promote ICC growth, MDSCs infiltration and angiogenesis, which was restored by adding exogenous CCL2. Furthermore, interestingly, the tumor-promoting effect of fibroblastic FAP is dependent on MDSCs via secretion of CCL2, as depletion of Gr-1+ cells reversed the restoring effects of exogenous CCL2 on tumor growth and angiogenesis. In vitro migration assay confirmed that exogenous CCL2 could rescue the impaired ability of ICC-Fbs to attract Gr-1+ cells caused by fibroblastic FAP knockdown. In contrast, fibroblastic FAP knockdown had no effect on...
Source: Neoplasia - Category: Cancer & Oncology Authors: Tags: Neoplasia Source Type: research