Asporin is a key stromal regulator of TGF-β-1 function in breast cancer (58.7)

Asporin is extracellular matrix protein that has been associated with bone and joint diseases. Using innovative proteomic analysis we have previously found asporin as overexpressed in pancreas and breast cancer. In the current work we explore for the first time the functional significance of asporin expression in cancer. We show in 150 cases of breast carcinoma that asporin is a consistent feature of the tumor, whose high levels positively correlate with the good patient outcome. On the molecular level we demonstrate that only tumor-associated fibroblasts are able to secrete asporin after being reprogrammed by the cancer cells. We found that TGF-β-1 alone is able to induce asporin expression and in turn asporin can bind TGF-β-1 to inhibit its action on TGF-β receptors. The main interaction between the two proteins occurs via asporin 159-205 amino acid region. Synthetic peptide corresponding to this key asporin segment is able to inhibit TGF-β-1 induction of SMAD2 phosphorylation in breast cancer cells. Us...