Toll Like Receptor-9 Mediated Invasion in Breast Cancer.

摘要

TLR9 is a cellular DNA-receptor that is widely expressed in breast cancers. The aim of this work was to study whether DNA derived from dead breast cancer cells can induce invasion in living breast cancer cells. In addition to showing previously that 'dead DNA' induces invasion in vitro, we discovered that TLR9 expression is hypoxia-regulated in breast cancer cells in vitro and in vivo. We also discovered that the lack of TLR9 results in a more aggressive tumor behavior in pre-clinical cancer models, but only in triple negative breast cancer cells. In line with these findings, we discovered that low TLR9 expression in breast tumors predicts poor prognosis, but only in patients with triple negative tumors. Our further pre-clinical experiments suggest that such poor prognosis may be due to an impaired immune-response at the tumor interface. Our results suggest that treatment induces the formation of DNA- structures which induces TLR9-mediated release of cytokines. Thus, our findings suggest that TLR9 expression and 'dead DNA' are biologically important in triple negative breast cancer.