TY - JOUR
T1 - Tumour-associated macrophage infiltration, neovascularization and aggressiveness in malignant melanoma
T2 - Role of monocyte chemotactic protein-1 and vascular endothelial growth factor-A
AU - Varney, Michelle L.
AU - Johansson, Sonny L.
AU - Singh, Rakesh K.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Melanoma
KW - Monocyte chemotactic protein-1 (MCP-1)
KW - Monocytes
KW - Tumour-associated macrophages
KW - Vascular endothelial growth factor
UR - http://www.scopus.com/inward/record.url?scp=27644590410&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=27644590410&partnerID=8YFLogxK
U2 - 10.1097/00008390-200510000-00010
DO - 10.1097/00008390-200510000-00010
M3 - Article
C2 - 16179869
AN - SCOPUS:27644590410
SN - 0960-8931
VL - 15
SP - 417
EP - 425
JO - Melanoma Research
JF - Melanoma Research
IS - 5
ER -