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Guo Q, Betts C, Pennock N, et al. Mammary Gland Involution Provides a Unique Model to Study the TGF-β Cancer Paradox. J Clin Med. 2017;6(1)doi: 10.3390/jcm6010010.
Guo, Q., Betts, C., Pennock, N., Mitchell, E., & Schedin, P. (2017). Mammary Gland Involution Provides a Unique Model to Study the TGF-β Cancer Paradox. Journal of clinical medicine, 6(1), . https://doi.org/10.3390/jcm6010010
Guo, Qiuchen, et al. "Mammary Gland Involution Provides a Unique Model to Study the TGF-β Cancer Paradox." Journal of clinical medicine vol. 6,1 (2017). doi: https://doi.org/10.3390/jcm6010010
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 Jan 13;6(1). doi: 10.3390/jcm6010010. PMID: 28098775; PMCID: PMC5294963.
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J Clin Med. 2017 Jan 13;6(1). doi: 10.3390/jcm6010010.

Mammary Gland Involution Provides a Unique Model to Study the TGF-β Cancer Paradox.

Journal of clinical medicine

Qiuchen Guo, Courtney Betts, Nathan Pennock, Elizabeth Mitchell, Pepper Schedin

Affiliations

  1. Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, OR 97239, USA. [email protected].
  2. Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, OR 97239, USA. [email protected].
  3. Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, OR 97239, USA. [email protected].
  4. Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, OR 97239, USA. [email protected].
  5. Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, OR 97239, USA. [email protected].
  6. Young Women's Breast Cancer Translational Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. [email protected].
  7. Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA. [email protected].

PMID: 28098775 PMCID: PMC5294963 DOI: 10.3390/jcm6010010

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.

Keywords: TGF-β; cancer; cellular crosstalk; weaning-induced mammary gland involution

Conflict of interest statement

The authors declare that they have no conflicts of interest. The founding sponsors had no role in writing of the manuscript.

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