title: Mammary Gland Involution Provides a Unique Model to Study the TGF-β Cancer Paradox.
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.
authors.affiliation: Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, OR 97239, USA. guo@ohsu.edu.
authors.forename: Qiuchen
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, OR 97239, USA. bettsc@ohsu.edu.
authors.forename: Courtney
authors.initials: C
authors.lastname: Betts
authors.affiliation: Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, OR 97239, USA. pennock@ohsu.edu.
authors.forename: Nathan
authors.initials: N
authors.lastname: Pennock
authors.affiliation: Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, OR 97239, USA. mitceliz@ohsu.edu.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Mitchell
authors.affiliation: Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, OR 97239, USA. Schedin@ohsu.edu.|Young Women's Breast Cancer Translational Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. Schedin@ohsu.edu.|Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA. Schedin@ohsu.edu.
authors.forename: Pepper
authors.initials: P
authors.lastname: Schedin
keywords: TGF-β; cancer; cellular crosstalk; weaning-induced mammary gland involution