Human endothelial cells express CCR2 and respond to MCP-1: Direct role of MCP-1 in angiogenesis and tumor progression

Rosalba Salcedo, Maria Lourdes Ponce, Howard A. Young, Ken Wasserman, Jerrold M. Ward, Hynda K. Kleinman, Joost J. Oppenheim, William J Murphy

Research output: Contribution to journalArticle

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Abstract

Although several CXC chemokines have been shown to induce angiogenesis and play roles in tumor growth, to date, no member of the CC chemokine family has been reported to play a direct role in angiogenesis. Here we report that the CC chemokine, monocyte chemotactic protein 1 (MCP-1), induced chemotaxis of human endothelial cells at nanomolar concentrations. This chemotactic response was inhibited by a monoclonal antibody to MCP-1. MCP-1 also induced the formation of blood vessels in vivo as assessed by the chick chorioallantoic membrane and the matrigel plug assays. As expected, the angiogenic response induced by MCP-1 was accompanied by an inflammatory response. With the use of a rat aortic sprouting assay in the absence of leukocytic infiltrates, we ruled out the possibility that the angiogenic effect of MCP-1 depended on leukocyte products. Moreover, the direct effect of MCP-1 on angiogenesis was consistent with the expression of CCR2, the receptor for MCP-1, on endothelial cells. Assessment of supernatant from a human breast carcinoma cell line demonstrated the production of MCP-1. Treatment of immunodeficient mice bearing human breast carcinoma cells with a neutralizing antibody to MCP-1 resulted in significant increases in survival and inhibition of the growth of lung micrometastases. Taken together, our data indicate that MCP-1 can act as a direct mediator of angiogenesis. As a chemokine that is abundantly produced by some tumors, it can also directly contribute to tumor progression. Therefore, therapy employing antagonists of MCP-1 in combination with other inhibitors of angiogenesis may achieve more comprehensive inhibition of tumor growth. (C) 2000 by The American Society of Hematology.

Original languageEnglish (US)
Pages (from-to)34-40
Number of pages7
JournalBlood
Volume96
Issue number1
StatePublished - Jul 1 2000
Externally publishedYes

Fingerprint

Chemokine CCL2
Endothelial cells
Tumors
Endothelial Cells
Neoplasms
CC Chemokines
Assays
Bearings (structural)
Growth
CCR2 Receptors
Cells
Breast Neoplasms
Chorioallantoic Membrane
CXC Chemokines
Neoplasm Micrometastasis
Angiogenesis Inhibitors
Blood vessels
Chemotaxis
Neutralizing Antibodies
Chemokines

ASJC Scopus subject areas

  • Hematology

Cite this

Salcedo, R., Ponce, M. L., Young, H. A., Wasserman, K., Ward, J. M., Kleinman, H. K., ... Murphy, W. J. (2000). Human endothelial cells express CCR2 and respond to MCP-1: Direct role of MCP-1 in angiogenesis and tumor progression. Blood, 96(1), 34-40.

Human endothelial cells express CCR2 and respond to MCP-1 : Direct role of MCP-1 in angiogenesis and tumor progression. / Salcedo, Rosalba; Ponce, Maria Lourdes; Young, Howard A.; Wasserman, Ken; Ward, Jerrold M.; Kleinman, Hynda K.; Oppenheim, Joost J.; Murphy, William J.

In: Blood, Vol. 96, No. 1, 01.07.2000, p. 34-40.

Research output: Contribution to journalArticle

Salcedo, R, Ponce, ML, Young, HA, Wasserman, K, Ward, JM, Kleinman, HK, Oppenheim, JJ & Murphy, WJ 2000, 'Human endothelial cells express CCR2 and respond to MCP-1: Direct role of MCP-1 in angiogenesis and tumor progression', Blood, vol. 96, no. 1, pp. 34-40.
Salcedo R, Ponce ML, Young HA, Wasserman K, Ward JM, Kleinman HK et al. Human endothelial cells express CCR2 and respond to MCP-1: Direct role of MCP-1 in angiogenesis and tumor progression. Blood. 2000 Jul 1;96(1):34-40.
Salcedo, Rosalba ; Ponce, Maria Lourdes ; Young, Howard A. ; Wasserman, Ken ; Ward, Jerrold M. ; Kleinman, Hynda K. ; Oppenheim, Joost J. ; Murphy, William J. / Human endothelial cells express CCR2 and respond to MCP-1 : Direct role of MCP-1 in angiogenesis and tumor progression. In: Blood. 2000 ; Vol. 96, No. 1. pp. 34-40.
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