Cancers 2011, 3(4), 3740-3761; doi:10.3390/cancers3043740
Review

Tumor-Associated Macrophages as Incessant Builders and Destroyers of the Cancer Stroma

1email, 1,†email, 1email, 1,2email and 1,* email
Received: 31 August 2011; in revised form: 15 September 2011 / Accepted: 19 September 2011 / Published: 28 September 2011
(This article belongs to the Special Issue Exploring Inflammation in Cancers)
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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
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

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.

AMA Style

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.

Chicago/Turabian Style

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.



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