Induction of inflammatory angiogenesis by monocyte chemoattractant protein-1.
Almost any growth of tumors is to some extent associated with an inflammatory reaction which may be anti-tumorigenic by acting directly on tumor cells or protumorigenic cells presumably by inducing tumor-associated angiogenesis. In this study, we have analyzed the angiogenesis-inducing capacity of monocyte chemoattractant protein-1 (MCP-1), a key regulatory molecule of monocyte trafficking to sites of inflammation. MCP-1 was found to be potently angiogenic when implanted into rabbit cornea, exerting potency similar to the specific angiogenic vascular endothelial growth factor (VEGF)-A(121). MCP-1-induced angiogenesis in the cornea is associated with prominent recruitment of macrophages, whereas VEGF-A(121)-induced corneal angiogenesis is devoid of inflammatory cell recruitment. Based on these findings, we studied MCP-1 expression and macrophage recruitment in human invasive ductal mammary carcinomas in comparison with the physiological angiogenic processes in bovine ovarian corpus luteum. Macrophage recruitment was always associated with MCP-1 expression. High macrophage counts in mammary tumors corresponded with poor prognosis. In contrast, physiological ovarian angiogenesis was associated with only minimal inflammatory recruitment of macrophages. Our data show that MCP-1 is an indirect inflammation-associated inducer of angiogenesis and demonstrate distinct qualitative differences between tumor angiogenesis in human mammary tumors and physiological angiogenesis in the ovary.
Cell Biology Laboratory, Department of Gynecology and Obstetrics, University of Göttingen Medical School, Göttingen, Germany.
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V
Goede
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L
Brogelli
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M
Ziche
H G
HG
Augustin
D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000098:blood supply / Q000473:pathology; D002417:Cattle; D018932:Chemokine CCL2 / Q000502:physiology*; D003315:Cornea / Q000098:blood supply; D003338:Corpus Luteum / Q000098:blood supply / Q000473:pathology; D016228:Endothelial Growth Factors / Q000502:physiology; D005260:Female; D006801:Humans; D008222:Lymphokines / Q000502:physiology; D008264:Macrophages / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D010053:Ovary / Q000098:blood supply / Q000473:pathology; D011817:Rabbits; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D018932:Chemokine CCL2; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors