Skin Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Skin Cancer, including details on identification, causes, prevention, treatment.

Analysis of gene expression in the tumor-associated macrophage.

Duff MD, Mestre J, Maddali S, Yan ZP, Stapleton P, Daly JM

Department of Surgery, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York, USA. mduff100@hotmail.com

INTRODUCTION: The tumor-associated macrophage (TAM) is at the front line of the host's defense against malignancy and provides an attractive target for immune-modulatory therapy. However, factors present within the tumor microenvironment can alter macrophage phenotype, preventing its cytotoxic activity and reducing its susceptibility to interferon-gamma and lipopolysaccharide-mediated stimulation. METHODS: Macrophages were isolated from subcutaneous B16 melanoma tumors implanted in C57 BL/6 mice. Wound macrophages were harvested from subcutaneously-implanted PVA sponges, and resting peritoneal macrophages were harvested by peritoneal lavage. Gene expression was analyzed using an Atlas cDNA array (Clontech, Mountain View, CA). RESULTS: TAM demonstrated a pattern of gene expression distinct from both wound and peritoneal macrophage. There is an increase in proliferation-associated genes and in genes encoding the ultrastructural proteins cofillin, zyxin, and vimentin more commonly associated with fibroblast-like cells. In addition, an observed decrease in expression of the CD14 gene, and increase in inhibitory pathways including osteopontin and its receptor CD44, the inositol 1,4,5-triphosphate receptor, and the receptors for interleukin-4 and granulocyte monocyte-colony stimulating factor could explain the resistance of TAM to lipopolysaccharide-mediated stimulation. There was also a significant decrease in the expression of the interferon-gamma second messenger, IRF-1. CONCLUSIONS: This study has identified a number of pathways involved in the suppression of TAM function. Targeting of these pathways may allow for the generation of more effective immune-modulatory anti-neoplastic therapy.

Published 24 August 2007 in J Surg Res, 142(1): 119-28.
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