Mesenchymal stem cells (MSCs) have been shown to localize to the tumor microenvironment and may contribute the tumor stroma. However the signals mediating this migratory process have not been fully defined. We used chromatographic fractionation to purify chemotactic factors produced by the breast carcinoma cell line, MDA-MB231. Two chromatographic steps including heparin and green dye columns as well as PAGE were used to enrich for factors that promote MSC migration in a transwell chamber assay. The resulting proteins were analyzed by tandem MS/MS micro-sequencing.Hepatoma-derived growth factor (HDGF) was identified as one of the major proteins in the enriched fraction. A specific antibody against HDGF blocked MSC migration toward tumor-conditioned medium in a dose-dependent manner. These data suggest that HDGF is a tumor-secreted signaling molecule that promotes migration of MSCs to the tumor microenvironment.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA