J. Cancer Mol. 2: 101-106, 2006

[Review Article]

Tumor-Associated Macrophage: Its Role in Cancer Invasion and Metastasis

Jin-Yuan Shih, Ang Yuan, Jeremy J.-W. Chen, and Pan-Chyr Yang

Department of Internal Medicine [J.-Y. Shih, P.-C. Yang] and Department of Emergency Medicine [A. Yuan], National Taiwan University Hospital, Taipei, Taiwan; Center for Genomic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan [J. J.-W. Chen, P.-C. Yang]; Institutes of Biomedical Sciences and Molecular Biology, National Chung-Hsing University, Taichung, Taiwan [J. J.-W. Chen] 

Abstract:

Cancer metastasis is not exclusively regulated by the deregulation of metastasis-promoting or suppressing genes in cancer cells.  The interaction between cancer cells and the stromal cells has been shown recently to promote cancer metastasis.  The macrophages within the tumor, referring to as tumour-associated macrophages (TAMs), are the pivotal member of stromal cells.  TAMs are derived from peripheral blood monocytes recruited into the tumor.  Upon activated by cancer cells, the TAMs can release a vast diversity of growth factors, proteolytic enzymes, cytokines, and inflammatory mediators.  Many of these factors are key agents in cancer metastasis.  The presence of extensive TAM infiltration has been shown to correlate with cancer metastasis and poor prognosis in a variety of human carcinomas.  TAMs promote cancer metastasis through several mechanisms including tumor angiogenesis, tumor growth, and tumor cell migration and invasion.  There are complex paracrine-signaling networks between TAMs and cancer cells to activate each other.  The colony-stimulating factor 1/epidermal growth factor paracrine loop is well known in regulation of breast cancer cells invasion.  TAMs-derived proteases, such as matrix metalloproteinases, urokinase-type plasminogen activator, and cathepsin B can promote cancer cells metastasis.  The roles of TAMs in epidermal-mesenchymal transition of cancer cells and resistance to cancer treatment are novel fields of study.  On the other hand, some investigations showed that the TAMs may play an important role in anti-tumor activity.  The control of TAMs to be pro-metastatic or tumoricidal is an important subject for cancer therapy.

Received 6/12/06; Revised 6/14/06; Accepted 6/14/06.

¹Correspondence: Dr. Pan-Chyr Yang, Department of Internal Medicine, or Dr. Ang Yuan, Department of Emergency Medicine, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 100, Taiwan.°@ Phone: 886-2-2356 2905. Fax: 886-2-2358 2867. E-mail: pcyang@ha.mc.ntu.edu.tw (Pan-Chyr Yang) or navy@ha.mc.ntu.edu.tw (Ang Yuan)

²Abbreviations: ECM, extracellular matrix; TAMs, tumor-associated macrophages; NSCLC, non-small cell lung cancer; CSF-1, colony-stimulating factor 1; VEGF, vascular endothelial growth factor; MIF, macrophage migration inhibition factor; PyMT, polyoma virus middle T oncoprotein; TNF-alpha, tumor-necrosis factor-alpha; MMPs, matrix metalloproteinases; EGF, epidermal growth factor; EMT, epithelial-mesenchymal transition.