Osteopontin as a multifaceted driver of bone metastasis and drug resistance

Metastasis to bone frequently occurs in majority of patients with advanced breast cancer and prostate cancer, leading to devastating skeletal-related events and substantially reducing the survival of patients. Currently, the crosstalk between tumor cells and the bone stromal compartment was widely investigated for bone metastasis and the resistance to many conventional therapeutic methods. Osteopontin (OPN), also known as SPP1 (secreted phosphoprotein 1), a secreted and chemokine-like glyco-phosphoprotein is involved in tumor progression such as cell proliferation, angiogenesis, and metastasis. The expression of OPN in tumor tissue and plasma has been clinically proved to be correlated to poor prognosis and shortened survival in patients with breast cancer and prostate cancer. This review summarizes the multifaceted roles that OPN plays in bone microenvironment and drug resistance, with emphasis on breast and prostate cancers, via binding to alpha v beta 3 integrin and CD44 receptor and inducing signaling cascades. We further discuss the promising therapeutic strategy for OPN targeting, mainly inhibiting OPN at transcriptional or protein level or blocking it binding to receptor or its downstream signaling pathways. The comprehending of the function of OPN in bone microenvironment is crucial for the development of novel biomarker and potential therapeutic target for the diagnosis and treatment of bone metastasis and against the emergence of drug resistance in advanced cancers.