Asporin Is a Fibroblast-Derived TGF-β1 Inhibitor and a Tumor Suppressor Associated with Good Prognosis in Breast Cancer

PLoS Medicine
Pamela MarisAndrei Turtoi

Abstract

Breast cancer is a leading malignancy affecting the female population worldwide. Most morbidity is caused by metastases that remain incurable to date. TGF-β1 has been identified as a key driving force behind metastatic breast cancer, with promising therapeutic implications. Employing immunohistochemistry (IHC) analysis, we report, to our knowledge for the first time, that asporin is overexpressed in the stroma of most human breast cancers and is not expressed in normal breast tissue. In vitro, asporin is secreted by breast fibroblasts upon exposure to conditioned medium from some but not all human breast cancer cells. While hormone receptor (HR) positive cells cause strong asporin expression, triple-negative breast cancer (TNBC) cells suppress it. Further, our findings show that soluble IL-1β, secreted by TNBC cells, is responsible for inhibiting asporin in normal and cancer-associated fibroblasts. Using recombinant protein, as well as a synthetic peptide fragment, we demonstrate the ability of asporin to inhibit TGF-β1-mediated SMAD2 phosphorylation, epithelial to mesenchymal transition, and stemness in breast cancer cells. In two in vivo murine models of TNBC, we observed that tumors expressing asporin exhibit significantly r...Continue Reading

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Citations

Jan 10, 2017·Journal of Clinical Medicine·Brunella CostanzaAndrei Turtoi
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Datasets Mentioned

BETA
GSE56265
GSE41445

Methods Mentioned

BETA
Protein Assay
ELISA
PCR
xenografts
xenograft

Software Mentioned

GOBO
ARRIVE
Kaplan Plotter
GraphPad
GraphPad Prism
Systat
SigmaPlot
ImageJ

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