TY - JOUR
T1 - Mammary gland involution provides a unique model to study the TGF-β cancer paradox
AU - Guo, Qiuchen
AU - Betts, Courtney
AU - Pennock, Nathan
AU - Mitchell, Elizabeth
AU - Schedin, Pepper
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
KW - Cancer
KW - Cellular crosstalk
KW - TGF-β
KW - Weaning-induced mammary gland involution
UR - http://www.scopus.com/inward/record.url?scp=85043623195&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85043623195&partnerID=8YFLogxK
U2 - 10.3390/jcm6010010
DO - 10.3390/jcm6010010
M3 - Review article
SN - 2077-0383
VL - 6
JO - Journal of Clinical Medicine
JF - Journal of Clinical Medicine
IS - 1
ER -