J. Cancer Mol. 2: 135-140, 2006

[Review Article]

Tumor-Associated Macrophage: Its Role in Tumor Angiogenesis

Chun-Chung Lee, Ko-Jiunn Liu, and Tze-Sing Huang

National Institute of Cancer Research, National Health Research Institutes, Taipei, Taiwan

Abstract:

Macrophages are important cells in wound healing, providing aids for tissue cell growth, tissue matrix remodeling and angiogenesis.  Solid tumor comprises not only tumor cells, but also tissue matrix and many stromal cells such as fibroblasts and macrophages.  Accumulating research results have suggested tumor-associated macrophages (TAMs) functioning in tumor cell proliferation, tumor cell migration and invasion, and tumor angiogenesis.  In this review article, we review data from clinical investigations and animal studies to demonstrate the association of TAMs with tumor angiogenesis.  We also discuss results of several mechanistic studies to provide possible mechanisms for TAMs-associated angiogenesis.  By interacting with cancer cells, TAMs can be induced to express more cytokines and tissue matrix-degrading enzymes, such as matrix metalloproteinases, plasminogen activators and cathepsin B, that are either direct angiogenic factors or tissue matrix modulators responsible for promoting tumor angiogenesis.  The angiogenic effect of TAMs can be neutralized by antagonizing antibodies or competitive soluble receptors of interleukin-6, interleukin-8 and tumor necrosis factor-alpha, suggesting the involvement of these cytokines in TAMs-associated angiogenesis.  With evidence indicating TAM’s tumor-promoting roles, many investigations have been undertaken to study the potential of using TAMs as the therapeutic target.  Photosensitizer can be labeled to the scavenger receptor class A to target TAMs in cancer photodynamic therapy.  In addition, macrophages can be engineered to serve as vehicles to carry drug or genes to the hypoxic areas of tumor.  More detailed mechanisms regarding the interaction between TAMs and tumor still need to be explored, and a thorough understanding of this interaction will provide some helpful conceptual suggestions for the future cancer therapy.

Received 7/18/06; Revised 8/2/06; Accepted 8/2/06

¹Correspondence: Dr. Tze-Sing Huang, National Institute of Cancer Research, National Health Research Institutes, 7F, No. 161, Min-Chuan East Road Section 6, Taipei 114, Taiwan, Republic of China. Phone: 886-2-2653 4401 ext 25138. Fax: 886-2-2792 9654. E-mail: tshuang@nhri.org.tw

²Abbreviations: TAMs, tumor-associated macrophages; MCP-1, monocyte chemotactic protein-1; GM-CSF, granulocyte-macrophage colony-stimulating factor; HIF, hypoxia-inducible factor; PyMT, polyoma virus middle T oncoprotein; CSF-1, colony-stimulating factor-1; VEGF, vascular endothelial growth factor; bFGF, basic fibroblast growth factor; EGF, epidermal growth factor; TGF-a, transforming growth factor-a; IL, interleukin; TNF-a, tumor necrosis factor-a; MMPs, matrix metalloproteinases; tPA, tissue-type plasminogen activator; uPA, urokinase-type plasminogen activator; TGF-b, transfoming growth factor-b.