Macrophages and chemokines as mediators of angiogenesis

Accumulating evidence attests to the important roles of both macrophages and chemokines in angiogenesis. Tumor-associated macrophages or TAMS constitute the major fraction of tumor-infiltrating leukocytes and are recruited by a number of chemoattractants chemoattractants that are produced by the tumor and tumor-associated stroma. This heterogeneous cell population is activated by a variety of stimuli and becomes polarized to result in functionally different phenotypes regarding tumor progression. As opposed to classically activated or M1 macrophages that exhibit anti-tumor functions, most TAMS are considered to be of the alternatively activated or M2 phenotype, and express multiple cytokines, proteases, and chemokines that promote tumor angiogenesis. Chemokines also have disparate effects on angiogenesis regulation, as several members of the CXC and CC chemokine families are potent inducers of angiogenesis, while a subset of CXC chemokines are angiostatic. This review summarizes the current literature regarding the roles and modes of action of macrophage-derived chemokines as mediators of angiogenesis.