Department of Pharmacy, Peking University First Hospital, Xicheng District, 10034, Beijing, China.
Department of Urology, Peking University First Hospital, Xicheng District, 10034, Beijing, China.
Pharmacol Res. 2019 Jun;144:235-244. doi: 10.1016/j.phrs.2019.04.030. Epub 2019 Apr 24.
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 αvβ3 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.
转移到骨骼中经常发生在大多数晚期乳腺癌和前列腺癌患者中，导致毁灭性的骨骼相关事件，并大大降低了患者的生存时间。目前，肿瘤细胞与骨基质细胞之间的串扰广泛地被研究用于骨转移和对许多常规治疗方法的耐药性。骨桥蛋白（OPN），也称为 SPP1（分泌型磷蛋白 1），是一种分泌型趋化因子样糖基磷蛋白，参与肿瘤的增殖、血管生成和转移等进展。肿瘤组织和血浆中 OPN 的表达已被临床证明与乳腺癌和前列腺癌患者的预后不良和生存时间缩短相关。这篇综述总结了 OPN 在骨微环境和耐药性中的多方面作用，重点讨论了乳腺癌和前列腺癌中，OPN 通过与αvβ3 整合素和 CD44 受体结合并诱导信号级联反应。我们进一步讨论了针对 OPN 的有前途的治疗策略，主要是在转录或蛋白水平上抑制 OPN，或阻断其与受体或其下游信号通路的结合。了解 OPN 在骨微环境中的功能对于开发新的生物标志物和潜在的治疗靶点，用于诊断和治疗骨转移以及对抗晚期癌症中耐药性的出现至关重要。
