"Combating Metastasis by Targeting Stromal Cells in Breast and Pancreatic Cancer"

Metastasis is a multi-step process that requires tumor cells to overcome substantial biologic barriers. Stromal cells contribute to multiple facets of the metastatic cascade and facilitate tumor cell success in overcoming the barriers that limit metastasis. Our laboratory studies cytokine/growth factor pathways in stromal cells that are critical to tumor cell metastasis in murine models of cancer. Two cytokines of particular interest are TGFβ and pleiotrophin (PTN). We have identified that TGFβ signaling within stromal cells participates directly in pancreatic tumor cell phenotype and metastasis. Additionally, we have found that PTN drives the acquisition of pro-metastatic macrophage phenotype in breast tumors. Studies that demonstrate each pathway is critical to tumor cell metastasis will be discussed. Overall, our results suggest that the therapeutic efficacy of anti-cancer strategies could be increased by including agents that inhibit the pro-metastatic activities of stromal cells.