Laboratory of Tumor Biology, Angiogenesis and Nanomedicine Research, National Centre for Cell Science (NCCS) , Pune 411007 , India
Expert Opin Ther Targets. 2014 Aug;18(8):883-95. doi: 10.1517/14728222.2014.925447. Epub 2014 Jun 4.
Cancer is a complex pathological disorder, established as a result of accumulation of genetic and epigenetic changes, which lead to adverse alterations in the cellular phenotype. Tumor progression involves intricate signaling mediated through crosstalk between various growth factors, cytokines and chemokines. Osteopontin (OPN), a chemokine-like protein, is involved in promotion of neoplastic cancer into higher grade malignancies by regulating various facets of tumor progression such as cell proliferation, angiogenesis and metastasis.
Tumors as well as stroma-derived OPN play key roles in various signaling pathways involved in tumor growth, angiogenesis and metastasis. OPN derived from tumor-activated macrophages modulates the tumor microenvironment and thereby regulate melanoma growth and angiogenesis. OPN also regulates hypoxia-inducible factor-1α-dependent VEGF expression leading to breast tumor growth and angiogenesis in response to hypoxia. Thus, a clear understanding of the molecular mechanism underlying OPN-mediated regulation will shed light on exciting avenues for further investigation of targeted therapies. Silencing of OPN using RNAi technology, blocking OPN activity using specific antibodies and small-molecule inhibitors might provide novel strategies, which would aid in developing effective therapeutics for the treatment of various types of cancer.
This review focuses on new possibilities to exploit OPN as a tumor and stroma-derived therapeutic target to combat cancer.
癌症是一种复杂的病理紊乱，是遗传和表观遗传变化积累的结果，导致细胞表型的不良改变。肿瘤的进展涉及通过各种生长因子、细胞因子和趋化因子之间的串扰进行的复杂信号转导。骨桥蛋白（OPN）是一种趋化因子样蛋白，通过调节肿瘤进展的各个方面，如细胞增殖、血管生成和转移，促进肿瘤向更高等级的恶性肿瘤发展。
肿瘤和基质来源的 OPN 在涉及肿瘤生长、血管生成和转移的各种信号通路中发挥关键作用。肿瘤激活的巨噬细胞衍生的 OPN 调节肿瘤微环境，从而调节黑色素瘤的生长和血管生成。OPN 还调节缺氧诱导因子-1α依赖性 VEGF 表达，导致乳腺癌在缺氧时的肿瘤生长和血管生成。因此，对 OPN 介导的调节的分子机制的清晰理解将为进一步研究靶向治疗提供令人兴奋的途径。使用 RNAi 技术沉默 OPN、使用特异性抗体和小分子抑制剂阻断 OPN 活性可能提供新的策略，有助于开发治疗各种类型癌症的有效疗法。
这篇综述重点介绍了将 OPN 作为肿瘤和基质来源的治疗靶点来对抗癌症的新可能性。
