NPNT promotes early-stage bone metastases in breast cancer by regulation of the osteogenic niche

Abstract

Patients with breast cancer are often afflicted by bone metastases, while the establishment and growth of bone metastases depend on interaction between cancer cells and the host environment. Moreover, osteoblasts, which play a vital role in cancer cells survival and colonization, can form an osteogenic niche in early stage of bone metastases. Also, it is widely accepted that there is a genetic determinant during bone metastases. Nephronectin (NPNT) is an extracellular matrix protein which has shown biological activities in breast cancer metastases and osteoblasts differentiation. But the role of NPNT in mediating breast cancer bone metastases remains elusive. In the present study, we revealed that up regulation of NPNT is associated with incidence of bone metastases. What's more, NPNT could significantly enhance the tumor cell clone formation but not proliferation and migration. We further demonstrated that NPNT significantly enhance osteoblast differentiation and tumor adhesion. Thus, we proposed that cancer secreted NPNT may be a novel marker with potential value of prediction and diagnosis of breast cancer bone metastases. Keyword: NPNT, Breast cancer, Bone metastases, Osteoblast