Figure 3. Macrophages Promote Seeding and Growth of Metastatic Cells.

Myeloid cells, most likely macrophages, are recruited to the pre-metastatic niche in response to secreted products from the primary tumor. The metastatic target organs contain fibroblasts and elaborate extracellular matrix consisting of fibronectin and collagen. These niches direct and enhance tumor cell seeding in sites distant from the primary tumor. Once the tumor cells arrive at the metastatic site and begin to extravasate they recruit macrophages that are differentiated from blood borne monocytes. These macrophages enhance the ability of tumors cells to extravasate and promote their subsequent survival and growth. They continue to accumulate in metastatic lesions where they stimulate the growth and survival of the metastatic cells. Several growth factors and signaling pathways are important for these macrophage functions including vascular endothelial growth factor (VEGF) in the pre-metastatic site and colony stimulating factor-1 (CSF-1) for growth of the tumor cells.