Tumour-associated macrophage infiltration,... : Melanoma Research (original) (raw)
ORIGINAL ARTICLES
Tumour-associated macrophage infiltration, neovascularization and aggressiveness in malignant melanoma: role of monocyte chemotactic protein-1 and vascular endothelial growth factor-A
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA
Sponsorship: This work was supported in part by grant CA72781 (R.K.S.) from the National Cancer Institute, National Institutes of Health and the Nebraska Research Initiative Molecular Therapeutics Program (R.K.S.).
Correspondence and requests for reprints to Rakesh K. Singh, Department of Pathology and Microbiology, The University of Nebraska Medical Center, 985845 Nebraska Medical Center, Omaha, NE 68198-5845, USA
Tel: 402 559 9949; fax: 402 559 5551;
e-mail: [email protected]
Received 12 October 2004 Accepted (after revision) 9 May 2005
Abstract
The objective of this study was to evaluate the role of tumour-associated macrophages (TAMs) in malignant melanoma progression, invasion and angiogenesis. We examined the levels of macrophage infiltration and monocyte chemotactic protein-1 (MCP-1), neovascularization and vascular endothelial growth factor-A (VEGF-A) in different Clark's level melanomas with varying thicknesses and metastases. The level of TAM density was significantly higher in thick (>0.75 mm) than thin (≤0.75 mm) melanomas, and positively correlated with melanoma invasiveness and metastasis. In contrast, MCP-1 expression was significantly lower in thick (>0.75 mm) than thin (≤0.75 mm) melanomas and negatively correlated with melanoma aggressiveness and invasion. We did not observe any significant difference in the levels of neovascularization between thin and thick melanomas, and no correlation with VEGF-A expression, TAM density or melanoma aggressiveness and invasion. Interestingly, levels of VEGF-A were significantly higher in metastatic melanoma than in thick melanoma. In addition, we observed lower levels of MCP-1 messenger RNA (mRNA) expression in more aggressive melanomas and in cell lines with higher metastatic potential. In summary, our data suggest a distinct pattern of TAM infiltration, MCP-1 expression, neovascularization and VEGF-A expression during human melanoma progression, and a complex interaction between TAMs and melanoma cells in the regulation of melanoma progression, angiogenesis and metastasis.
© 2005 Lippincott Williams & Wilkins, Inc.