%0 Journal Article
%T Bone marrow¨Cderived fibroblasts are a functionally distinct stromal cell population in breast cancer
%J JEM | The Journal of Experimental Medicine
%D 2018
%R 10.1084/jem.20180818
%X Cancer-associated fibroblasts (CAFs) are highly prominent in breast tumors, but their functional heterogeneity and origin are still largely unresolved. We report that bone marrow (BM)¨Cderived mesenchymal stromal cells (MSCs) are recruited to primary breast tumors and to lung metastases and differentiate to a distinct subpopulation of CAFs. We show that BM-derived CAFs are functionally important for tumor growth and enhance angiogenesis via up-regulation of Clusterin. Using newly generated transgenic mice and adoptive BM transplantations, we demonstrate that BM-derived fibroblasts are a substantial source of CAFs in the tumor microenvironment. Unlike resident CAFs, BM-derived CAFs do not express PDGFR¦Á, and their recruitment resulted in a decrease in the percentage of PDGFR¦Á-expressing CAFs. Strikingly, decrease in PDGFR¦Á in breast cancer patients was associated with worse prognosis, suggesting that BM-derived CAFs may have deleterious effects on survival. Therefore, PDGFR¦Á expression distinguishes two functionally unique CAF populations in breast tumors and metastases and may have important implications for patient stratification and precision therapeutics.
%U http://jem.rupress.org/content/215/12/3075