PMID- 10891427
OWN - NLM
STAT- MEDLINE
DCOM- 20000810
LR  - 20220409
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 96
IP  - 1
DP  - 2000 Jul 1
TI  - Human endothelial cells express CCR2 and respond to MCP-1: direct role of MCP-1 
      in angiogenesis and tumor progression.
PG  - 34-40
AB  - 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.
FAU - Salcedo, R
AU  - Salcedo R
AD  - Laboratory of Molecular Immunoregulation, Laboratory of Experimental Immunology, 
      Division of Basic Sciences; Intramural Research Support Program, SAIC, Frederick, 
      MD, USA.
FAU - Ponce, M L
AU  - Ponce ML
FAU - Young, H A
AU  - Young HA
FAU - Wasserman, K
AU  - Wasserman K
FAU - Ward, J M
AU  - Ward JM
FAU - Kleinman, H K
AU  - Kleinman HK
FAU - Oppenheim, J J
AU  - Oppenheim JJ
FAU - Murphy, W J
AU  - Murphy WJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (CCR2 protein, human)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Ccr2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Drug Combinations)
RN  - 0 (Laminin)
RN  - 0 (Proteoglycans)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - 119978-18-6 (matrigel)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Allantois/blood supply
MH  - Animals
MH  - Breast Neoplasms/*blood supply/drug therapy/pathology
MH  - Cell Division/drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/*pharmacology
MH  - Chemotaxis/drug effects/*physiology
MH  - Chick Embryo
MH  - Chorion/blood supply
MH  - Collagen
MH  - Drug Combinations
MH  - Endothelium, Vascular/drug effects/*physiology
MH  - Extracellular Matrix
MH  - Female
MH  - Humans
MH  - Laminin
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, SCID
MH  - Neovascularization, Pathologic/pathology/*prevention & control
MH  - Neovascularization, Physiologic/drug effects/*physiology
MH  - Proteoglycans
MH  - Rats
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/genetics/*physiology
MH  - Transplantation, Heterologous
MH  - Tumor Cells, Cultured
MH  - Umbilical Veins
EDAT- 2000/07/13 11:00
MHDA- 2000/08/12 11:00
CRDT- 2000/07/13 11:00
PHST- 2000/07/13 11:00 [pubmed]
PHST- 2000/08/12 11:00 [medline]
PHST- 2000/07/13 11:00 [entrez]
AID - S0006-4971(20)72127-0 [pii]
PST - ppublish
SO  - Blood. 2000 Jul 1;96(1):34-40.