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.
Goede
V
V
Cell Biology Laboratory, Department of Gynecology and Obstetrics, University of Göttingen Medical School, Göttingen, Germany.
Brogelli
L
L
Ziche
M
M
Augustin
H G
HG
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