Induction of inflammatory angiogenesis by monocyte chemoattractant protein-1

Almost any growth of tumors is to some extent associated with an inflammato ry reaction which may be anti-tumorigenic by acting directly on tumor cells or protumorigenic cells presumably by inducing tumor-associated angiogenes is. In this study, we have analyzed the angiogenesis-inducing capacity of m onocyte chemoattractant protein-1 (MCP-1), a key regulatory molecule of mon ocyte trafficking to sites of inflammation. MCP-1 was found to be potently angiogenic when implanted into rabbit cornea, exerting potency similar to t he specific angiogenic vascular endothelial growth factor (VEGF)-A(121). MC P-1-induced angiogenesis in the cornea is associated with prominent recruit ment of macrophages, whereas VEGF-A(121)-induced corneal angiogenesis is de void of inflammatory cell recruitment. Based on these findings, we studied MCP-1 expression and macrophage recruitment in human invasive ductal mammar y carcinomas in comparison with the physiological angiogenic processes in b ovine ovarian corpus luteum, Macrophage recruitment was always associated w ith MCP-1 expression. High macrophage counts in mammary tumors corresponded with poor prognosis. In contrast, physiological ovarian angiogenesis was a ssociated with only minimal inflammatory recruitment of macrophages. Our da ta show that MCP-1 is an indirect inflammation-associated inducer of angiog enesis and demonstrate distinct qualitative differences between tumor angio genesis in human mammary tumors and physiological angiogenesis in the ovary . Int. J. Cancer 82:765-770, 1999, (C) 1999 Wiley-Liss. Inc.