Induction of inflammatory angiogenesis by monocyte chemoattractant protein-1

Int J Cancer. 1999 Aug 27;82(5):765-70. doi: 10.1002/(sici)1097-0215(19990827)82:5<765::aid-ijc23>;2-f.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / blood supply
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / blood supply
  • Carcinoma, Ductal, Breast / pathology
  • Cattle
  • Chemokine CCL2 / physiology*
  • Cornea / blood supply
  • Corpus Luteum / blood supply
  • Corpus Luteum / pathology
  • Endothelial Growth Factors / physiology
  • Female
  • Humans
  • Lymphokines / physiology
  • Macrophages / physiology
  • Neovascularization, Pathologic / physiopathology*
  • Ovary / blood supply
  • Ovary / pathology
  • Rabbits
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Chemokine CCL2
  • Endothelial Growth Factors
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors