Tumor-promoting properties of stromal fibroblasts in invasive human mammary carcinomas

Over the past three decades, the research of human cancers has focused on carcinoma cells. However, tumor is, in fact, highly complex tissues, recruiting non-carcinoma cell comportments, such as inflammatory cells, fibroblasts, or endothelial cells. Fibroblasts often constitute the majority of the stromal cells within breast carcinoma, yet the functional contributions of these cells to tumorigenesis are poorly understood. The carcinoma-associated fibroblasts (CAFs) extracted from invasive human breast carcinoma masses maintain traits of myofibroblasts and promote the growth of admixed human breast carcinoma cells in a co-implantation tumor xenograft model. Stromal cell-derived factor 1 (SDF-1), which is secreted at elevated levels by CAFs, plays a central role in this promotion of tumor growth, acting through both paracrine and endocrine mechanisms. CAF-secreted SDF-1 stimulates tumor growth directly through the cognate receptor, CXCR4, which is expressed by carcinoma cells. Moreover, CAFs promote angiogenesis through their enhanced ability to recruit endothelial progenitor cells into carcinomas, an effect mediated in part by SDF-1. These findings indicate that SDF-1 is critical to the tumor-promoting effects of the stromal fibroblasts present within invasive human breast carcinomas.