Chemokines and Receptors in Angiogenesis
Chemokines are a large superfamily of mostly small, secreted chemotactic cytokines that have a well-characterized ability to recruit leukocytes to sites of inflammation. A subset of these factors has also been found to be involved in regulating the angiogenic activities of endothelial cells under both physiological and pathological conditions such as wound healing, chronic inflammation, and tumor growth. Chemokines of the CXC family are characterized by a Cysteine-X-Cysteine (CXC) motif at their amino terminal ends and act as potent inducers or inhibitors of angiogenesis. Those containing the amino acids Glutamic acid-Leucine-Arginine (ELR) adjacent to the CXC motif bind to the CXCR2 receptor and promote angiogenesis, while those lacking the ELR motif primarily bind to CXCR3 and inhibit angiogenesis. A few of the CC chemokines, most notably CCL2, have also been shown to stimulate angiogenesis. Several studies demonstrate a correlation between the levels of angiogenic chemokines and tumor angiogenesis. Likewise, depletion of angiogenic chemokines in different forms of cancer has been shown to reduce tumor angiogenesis and metastatic potential.