Targeting tumor-associated macrophages and inhibition of MCP-1 reduce angiogenesis and tumor growth in a human melanoma xenograft

J Invest Dermatol. 2007 Aug;127(8):2031-41. doi: 10.1038/sj.jid.5700827. Epub 2007 Apr 26.


Chemokines such as monocyte chemoattractant protein (MCP)-1 are key agonists that attract macrophages to tumors. In melanoma, it has been previously shown that variable levels of MCP-1/CCL2 appear to correlate with infiltrating macrophages and tumor fate, with low to intermediate levels of the chemokine contributing to melanoma development. To work under such conditions, a poorly tumorigenic human melanoma cell line was transfected with an expression vector encoding MCP-1. We found that M2 macrophages are associated to MCP-1+ tumors, triggering a profuse vascular network. To target the protumoral macrophages recruitment and reverting tumor growth promotion, clodronate-laden liposomes (Clod-Lip) or bindarit were administered to melanoma-bearing mice. Macrophage depletion after Clod-Lip treatment induced development of smaller tumors than in untreated mice. Immunohistochemical analysis with an anti-CD31 antibody revealed scarce vascular structures mainly characterized by narrow vascular lights. Pharmacological inhibition of MCP-1 with bindarit also reduced tumor growth and macrophage recruitment, rendering necrotic tumor masses. We suggest that bindarit or Clod-Lip abrogates protumoral-associated macrophages in human melanoma xenografts and could be considered as complementary approaches to antiangiogenic therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Chemokine CCL2 / antagonists & inhibitors*
  • Chemokine CCL2 / physiology
  • Clodronic Acid / administration & dosage*
  • Humans
  • Indazoles / therapeutic use*
  • Liposomes
  • Macrophages / physiology*
  • Male
  • Melanoma, Experimental / blood supply
  • Melanoma, Experimental / drug therapy*
  • Mice
  • Neoplasm Transplantation
  • Neovascularization, Pathologic / drug therapy*
  • Platelet Endothelial Cell Adhesion Molecule-1 / analysis
  • Propionates / therapeutic use*
  • Transplantation, Heterologous


  • Chemokine CCL2
  • Indazoles
  • Liposomes
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Propionates
  • Clodronic Acid
  • bindarit