Hematopoietic stem cell derived carcinoma-associated fibroblasts: a novel origin

Researchers have begun to appreciate the significant role that the microenvironment plays in tumorigenesis and are now shedding light on the role of the stroma in induction and progression of solid tumors. While the stroma of solid tumors is comprised of many cell types, including vascular and immune cells, one of the most prominent cell types in the tumor stroma is the fibroblast, called the carcinoma-associated fibroblast (CAF) or tumor-associated fibroblast (TAF). The interaction between CAFs and tumor cells is quite complex. CAFs have been implicated in tumor angiogenesis, immunosuppression, tumor cell proliferation and aggressiveness, genetic instability, and metastasis. However, their specific roles in each of these processes have only been partially elucidated. Determining the role of CAFs has been complicated by the fact that researchers have demonstrated heterogeneity in the stromal fibroblast population. This heterogeneity has brought about the concept of multiple origins for CAFs. While many origins of CAFs have been suggested, in our own laboratory we have identified a novel hematopoietic stem cell (HSC) origin of CAFs. Given the profound role of CAFs in tumor progression and prognosis, the CAF represents an exciting potential therapeutic target. The heterogeneity of the CAF population makes research directed at investigating the roles and origins of CAFs critical to development of such anti-tumor therapies.