Macrophages: Regulators of the Inflammatory Microenvironment during Mammary Gland Development and Breast Cancer

Figure 2

Complex interactions in the tumor microenvironment. Breast cancer cells located in the tumor periphery (red rectangles) secrete cytokines and chemokines, which recruit monocytes from the circulation and differentiate them into tumor-associated macrophages (TAMs). Tumor cells located in the inner, hypoxic region (blue rectangles) develop a more specialized array of molecules to recruit macrophages poised to help the hypoxic cells survive and proliferate. The stromal cells of the tumor, along with components of the extracellular matrix (such as collagen I and hyaluronan), additionally contribute to the recruitment and retention of TAMs. Once educated by the tumor microenvironment, TAMs upregulate pathways associated with both M1- and M2-activated macrophages and actively support the survival, proliferation, and metastasis of breast cancer cells.