Toll-Like Receptor Pathway as Mediator of Bisphosphonate Effects in Breast Cancer

摘要

Bisphosphonates (BPs, i.e. clodronate and zoledronate) are frequently used in the treatment of breast cancer, once bone metastases have occurred. These drugs inhibit cancer-induced bone complications, because they inhibit the bone resorbing osteoclasts. Less is known about the direct effects of BPs on breast cancer cells. The aim of this work was to study the possibility that some of the BP-induced effects in breast cancer cells might be mediated via the Toll-like receptor pathway. We discovered that human breast cancer cell lines exhibit variable expression of Toll-like receptor 9 (TLR9) Expression of TLR9 was associated with increased invasiveness upon stimulation of the cells with TLR9 agonists. Since similar effects were also seen in other types of cancer cells that express TLR9, this may represent a novel mechanism through which bacterial infections promote cancer progression.