J. Clin. Med. 2017, 6(1), 10; https://doi.org/10.3390/jcm6010010
Mammary Gland Involution Provides a Unique Model to Study the TGF-β Cancer Paradox
1
Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, OR 97239, USA
2
Young Women’s Breast Cancer Translational Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
3
Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA
†
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Andrei Turtoi
Received: 13 November 2016 / Revised: 21 December 2016 / Accepted: 27 December 2016 / Published: 13 January 2017
(This article belongs to the Special Issue Biological and Clinical Aspects of TGF-beta in Carcinogenesis)
Abstract
Transforming Growth Factor-β (TGF-β) signaling in cancer has been termed the “TGF-β paradox”, acting as both a tumor suppresser and promoter. The complexity of TGF-β signaling within the tumor is context dependent, and greatly impacted by cellular crosstalk between TGF-β responsive cells in the microenvironment including adjacent epithelial, endothelial, mesenchymal, and hematopoietic cells. Here we utilize normal, weaning-induced mammary gland involution as a tissue microenvironment model to study the complexity of TGF-β function. This article reviews facets of mammary gland involution that are TGF-β regulated, namely mammary epithelial cell death, immune activation, and extracellular matrix remodeling. We outline how distinct cellular responses and crosstalk between cell types during physiologically normal mammary gland involution contribute to simultaneous tumor suppressive and promotional microenvironments. We also highlight alternatives to direct TGF-β blocking anti-cancer therapies with an emphasis on eliciting concerted microenvironmental-mediated tumor suppression. View Full-Text
Graphical abstract
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 (CC BY 4.0).
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Guo, Q.; Betts, C.; Pennock, N.; Mitchell, E.; Schedin, P. Mammary Gland Involution Provides a Unique Model to Study the TGF-β Cancer Paradox. J. Clin. Med. 2017, 6, 10.
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