TGF-β, Bone Morphogenetic Protein, and Activin Signaling and the Tumor Microenvironment.

Published on May 1, 2017in Cold Spring Harbor Perspectives in Biology10.005
· DOI :10.1101/CSHPERSPECT.A022285
Michael W. Pickup23
Estimated H-index: 23
(Vandy: Vanderbilt University),
Philip Owens26
Estimated H-index: 26
(Vandy: Vanderbilt University),
Harold L. Moses125
Estimated H-index: 125
(Vandy: Vanderbilt University)
Sources
Abstract
Abstract The cellular and noncellular components surrounding the tumor cells influence many aspects of tumor progression. Transforming growth factor β (TGF-β), bone morphogenetic proteins (BMPs), and activins have been shown to regulate the phenotype and functions of the microenvironment and are attractive targets to attenuate protumorigenic microenvironmental changes. Given the pleiotropic nature of the cytokines involved, a full understanding of their effects on numerous cell types in many contexts is necessary for proper clinical intervention. In this review, we will explore the various effects of TGF-β, BMP, and activin signaling on stromal phenotypes known to associate with cancer progression. We will summarize these findings in the context of their tumor suppressive or promoting effects, as well as the molecular changes that these cytokines induce to influence stromal phenotypes.
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References185
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Bone morphogenetic proteins (BMPs) are secreted cytokines/growth factors that have differing roles in cancer. BMPs are overexpressed in human breast cancers, but loss of BMP signaling in mammary carcinomas can accelerate metastasis. We show that human breast cancers display active BMP signaling, which is rarely downregulated or homozygously deleted. We hypothesized that systemic inhibition of BMP signaling in both the tumor and the surrounding microenvironment could prevent tumor progression and...
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Transforming growth factor-beta (TGF-β) is a pleiotropic cytokine with the capability to act as tumour suppressor or tumour promoter depending on the cellular context. TGF-beta receptor type-2 (TGFBR2) is the ligand-binding receptor for all members of the TGF-β family. Data from mouse model experiments demonstrated that loss of Tgfbr2 expression in mammary fibroblasts was linked to tumour initiation and metastasis. Using a randomised tamoxifen trial cohort including in total 564 invasive breast ...
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Bone Morphogenetic Protein (BMP) receptors mediate a diverse range of signals to regulate both development and disease. BMP activity has been linked to both tumor promoting and suppressive functions in both tumor cells and their surrounding microenvironment. We sought to investigate the requirement for BMPR2 in stromal fibroblasts during mammary tumor formation and metastasis. We utilized FSP1 (Fibroblast Specific Protein-1) promoter driven Cre to genetically delete BMPR2 in mice expressing the ...
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