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The Scientific World Journal
Volume 2014, Article ID 521754, 14 pages
Review Article

Transforming Growth Factor-Beta and Matrix Metalloproteinases: Functional Interactions in Tumor Stroma-Infiltrating Myeloid Cells

Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Dr Subotića 4, 11129 Belgrade, Serbia

Received 30 August 2013; Accepted 28 October 2013; Published 21 January 2014

Academic Editors: E. Ayroldi, D. Cataldo, and T. Quan

Copyright © 2014 Jelena Krstic and Juan F. Santibanez. 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.


Transforming growth factor-beta (TGF-β) is a pleiotropic factor with several different roles in health and disease. In tumorigenesis, it may act as a protumorigenic factor and have a profound impact on the regulation of the immune system response. Matrix metalloproteinases (MMPs) are a family that comprises more than 25 members, which have recently been proposed as important regulators acting in tumor stroma by regulating the response of noncellular and cellular microenvironment. Tumor stroma consists of several types of resident cells and infiltrating cells derived from bone marrow, which together play crucial roles in the promotion of tumor growth and metastasis. In cancer cells, TGF-β regulates MMPs expression, while MMPs, produced by either cancer cells or residents’ stroma cells, activate latent TGF-β in the extracellular matrix, together facilitating the enhancement of tumor progression. In this review we will focus on the compartment of myeloid stroma cells, such as tumor-associated macrophages, neutrophils, and dendritic and mast cells, which are potently regulated by TGF-β and produce large amounts of MMPs. Their interplay and mutual implications in the generation of pro-tumorigenic cancer microenvironment will be analyzed.