Tumor-associated macrophage-induced invasion and angiogenesis of human basal cell carcinoma cells by cyclooxygenase-2 induction

J Invest Dermatol. 2009 Apr;129(4):1016-25. doi: 10.1038/jid.2008.310. Epub 2008 Oct 9.


Tumor-associated macrophages (TAMs) and cyclooxygenase-2 (COX-2) are associated with invasion, angiogenesis, and poor prognosis in many human cancers. However, the role of TAMs in human basal cell carcinoma (BCC) remains elusive. We found that the number of TAMs infiltrating the tumor is correlated with the depth of invasion, microvessel density, and COX-2 expression in human BCC cells. TAMs also aggregate near COX-2 expressing BCC tumor nests. We hypothesize that TAMs might activate COX-2 in BCC cells and subsequently increase their invasion and angiogenesis. TAMs are a kind of M2 macrophage derived from macrophages exposed to Th2 cytokines. M2-polarized macrophages derived from peripheral blood monocytes were cocultured with BCC cells without direct contact. Coculture with the M2 macrophages induced COX-2-dependent invasion and angiogenesis of BCC cells. Human THP-1 cell line cells, after treated with phorbol myristate acetate (PMA), differentiated to macrophages with M2 functional profiles. Coculture with PMA-treated THP-1 macrophages induced COX-2-dependent release of matrix metalloproteinase-9 and subsequent increased invasion of BCC cells. Macrophages also induced COX-2-dependent secretion of basic fibroblast growth factor and vascular endothelial growth factor-A, and increased angiogenesis in BCC cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Basal Cell / blood supply*
  • Carcinoma, Basal Cell / pathology*
  • Cell Line, Tumor
  • Cell Polarity
  • Cyclooxygenase 2 / biosynthesis*
  • Enzyme Induction
  • Fibroblast Growth Factor 2 / biosynthesis
  • Humans
  • Macrophages / physiology*
  • Matrix Metalloproteinase 9 / biosynthesis
  • NF-kappa B / metabolism
  • Neoplasm Invasiveness
  • Neovascularization, Pathologic / etiology*
  • Skin Neoplasms / blood supply*
  • Skin Neoplasms / pathology*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Vascular Endothelial Growth Factor A / biosynthesis
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • NF-kappa B
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • p38 Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 9
  • Tetradecanoylphorbol Acetate