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Tumor-Associated Macrophages as Incessant Builders and Destroyers of the Cancer Stroma
Department of Immunology and Inflammation Istituto Clinico Humanitas, Via Manzoni 113, Rozzano-Milano 20089, Italy
Department of Translational Medicine, University of Milano, Milano 20089, Italy
Present address: University of California, San Francisco, CA 94102-6232, USA.
* Author to whom correspondence should be addressed.
Received: 31 August 2011; in revised form: 15 September 2011 / Accepted: 19 September 2011 / Published: 28 September 2011
Abstract: Tumor-Associated Macrophages (TAM) are key components of the reactive stroma of tumors. In most, although not all cancers, their presence is associated with poor patient prognosis. In addition to releasing cytokines and growth factors for tumor and endothelial cells, a distinguished feature of TAM is their high-rate degradation of the extra-cellular matrix. This incessant stroma remodelling favours the release of matrix-bound growth factors and promotes tumor cell motility and invasion. In addition, TAM produce matrix proteins, some of which are typical of the neoplastic tissues. The gene expression profile of TAM isolated from human tumors reveals a matrix-related signature with the up-regulation of genes coding for different matrix proteins, as well as several proteolytic enzymes. Among ECM components are: osteopontin, osteoactivin, collagens and fibronectin, including also a truncated isoform of fibronectin termed migration stimulation factor. In addition to serve as structural proteins, these matrix components have key functions in the regulation of the vessel network, in the inductionof tumor cell motility and degradation of cellular debris. Among proteolytic enzymes are: matrix metalloproteases, cathepsins, lysosomal and ADAM proteases, and the urokinase-type plasminogen activator. The degrading activity of TAM, coupled to the production of bio-active ECM proteins, co-operate to the build-up and maintenance of an inflammatory micro-environment which eventually promotes tumor progression.
Keywords: Tumor-Associated Macrophages (TAM); extra-cellular matrix (ECM); stroma; proteases; MMPs; cancer; inflammation
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Liguori, M.; Solinas, G.; Germano, G.; Mantovani, A.; Allavena, P. Tumor-Associated Macrophages as Incessant Builders and Destroyers of the Cancer Stroma. Cancers 2011, 3, 3740-3761.
Liguori M, Solinas G, Germano G, Mantovani A, Allavena P. Tumor-Associated Macrophages as Incessant Builders and Destroyers of the Cancer Stroma. Cancers. 2011; 3(4):3740-3761.
Liguori, Manuela; Solinas, Graziella; Germano, Giovanni; Mantovani, Alberto; Allavena, Paola. 2011. "Tumor-Associated Macrophages as Incessant Builders and Destroyers of the Cancer Stroma." Cancers 3, no. 4: 3740-3761.