Analysis of Gene Expression in the Tumor-Associated Macrophage

• Published in: The Journal of surgical research 2007-09, Vol.142 (1), p.119-128
• Main Authors: Duff, Michael D., M.Ch. A.F.R.C.S.I, Mestre, Juan, M.D, Maddali, Sirish, M.D, Yan, Zhao Ping, M.D, Stapleton, Philip, M.D., Ph.D, Daly, John M., M.D
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Proliferation; Dermatology; Extracellular Matrix - metabolism; Extracellular Matrix - pathology; Female; gene array; Gene Expression Profiling; General aspects; Macrophages - metabolism; Macrophages - pathology; Macrophages, Peritoneal - metabolism; Macrophages, Peritoneal - pathology; Medical sciences; melanoma; Melanoma, Experimental - metabolism; Melanoma, Experimental - pathology; Mice; Mice, Inbred C57BL; Oligonucleotide Array Sequence Analysis; Peritoneal Lavage; RNA, Messenger - genetics; RNA, Messenger - metabolism; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; Surgery; Surgical Sponges - adverse effects; tumor-associated macrophage; Tumors of the skin and soft tissue. Premalignant lesions; Wounds and Injuries - etiology; Wounds and Injuries - metabolism; Wounds and Injuries - pathology
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2006.12.542

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-γ 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-γ 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.