Abstract
With the recent addition of anti-angiogenic agents to cancer treatment, the angiogenesis regulators in platelets are gaining importance. Platelet factor 4 (PF-4/CXCL4) and Connective tissue activating peptide III (CTAP-III) are two platelet-associated chemokines that modulate tumor angiogenesis, inflammation within the tumor microenvironment, and in turn tumor growth. Here, we review the role of PF-4 and CTAP-III in the regulation of tumor angiogenesis; the results of clinical trial using recombinant PF-4 (rPF-4); and the use of PF-4 and CTAP-III as cancer biomarkers.
Highlights
Angiogenesis regulators are sequestered in platelets [1]
We have summarized emerging data on role of PF-4 and CTAP-III in regulation of tumor growth
It appears that the role of these two chemokines in modulation of tumor dynamics cannot be separated from the role of platelets and inflammation within the tumor microenvironment
Summary
Angiogenesis regulators are sequestered in platelets [1]. Platelet factor 4 and Connective tissue activating peptide III constitute two major platelet CXC chemokines [2]. It has been shown that continuous accumulation of NAP-2, as a product of PBP and CTAP-III proteolysis, results in antiinflammatory activity by desensitization of neutrophils through down-regulation of chemokine receptors, especially CXCR-2. This finding suggests that NAP-2 has dual function and that interaction of the various PBP cleavage products produces a very finely tuned system. (8) The remodeled ECM at the side of inflammation and angiogenesis enables the interaction of the released growth factors (e.g. VEGF) with their respective receptors and leads to modulation of angiogenesis and regulation of tumor spreading [53]; (9) CTAP-III stimulates further GAG synthesis [54] on the surface of endothelial cell injury leading to increased PF-4 production and localization of heparin binding angiogenesis regulators. It is likely that PF-4 rather than being released from platelets in circulation, binds locally to the HS at sites of platelet adhesion
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