Figure 1: The primary tumor microenvironment. Cancer cells in primary tumors are surrounded by a complex microenvironment that consists of numerous cells, including endothelial cells of the blood vessel, cancer-associated fibroblast, lymphocytes, neutrophil, MSCs, macrophages, cancer stem cells, and pericytes. Solid tumors contain a significant fraction of microregions that are chronically or transiently hypoxic, in which HIF-1 associated signaling pathway is activated, thus inducing the expression of various downstream genes, including VEGF and SDF-1.