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Mediators of Inflammation
Volume 2017, Article ID 9294018, 13 pages
https://doi.org/10.1155/2017/9294018
Review Article

Inflammation and Cancer: Extra- and Intracellular Determinants of Tumor-Associated Macrophages as Tumor Promoters

1Avidin Ltd., Alsó Kikötő sor 11/D., Szeged 6726, Hungary
2Synaptogenex Ltd., Őzsuta utca 20995/1, Budapest 1037, Hungary
3Department of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, Temesvári krt. 62, Szeged 6726, Hungary
4Department of Genetics, Biological Research Center, Hungarian Academy of Sciences, Temesvári krt. 62, Szeged 6726, Hungary

Correspondence should be addressed to Gabor J. Szebeni; moc.hcetoibnidiva@inebezs.g

Received 25 August 2016; Accepted 26 December 2016; Published 18 January 2017

Academic Editor: Yona Keisari

Copyright © 2017 Gabor J. Szebeni et al. 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.

Abstract

One of the hallmarks of cancer-related inflammation is the recruitment of monocyte-macrophage lineage cells to the tumor microenvironment. These tumor infiltrating myeloid cells are educated by the tumor milieu, rich in cancer cells and stroma components, to exert functions such as promotion of tumor growth, immunosuppression, angiogenesis, and cancer cell dissemination. Our review highlights the ontogenetic diversity of tumor-associated macrophages (TAMs) and describes their main phenotypic markers. We cover fundamental molecular players in the tumor microenvironment including extra- (CCL2, CSF-1, CXCL12, IL-4, IL-13, semaphorins, WNT5A, and WNT7B) and intracellular signals. We discuss how these factors converge on intracellular determinants (STAT3, STAT6, STAT1, NF-κB, RORC1, and HIF-1α) of cell functions and drive the recruitment and polarization of TAMs. Since microRNAs (miRNAs) modulate macrophage polarization key miRNAs (miR-146a, miR-155, miR-125a, miR-511, and miR-223) are also discussed in the context of the inflammatory myeloid tumor compartment. Accumulating evidence suggests that high TAM infiltration correlates with disease progression and overall poor survival of cancer patients. Identification of molecular targets to develop new therapeutic interventions targeting these harmful tumor infiltrating myeloid cells is emerging nowadays.