Harrington Laboratory for Molecular Orthopedics, Department of Orthopedic Surgery, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA; University of Kansas Cancer Center, Kansas City, KS 66160, USA.
Crit Rev Oncol Hematol. 2014 Feb;89(2):330-41. doi: 10.1016/j.critrevonc.2013.08.013. Epub 2013 Sep 7.
The mechanisms underlying malignant cell metastasis to secondary sites such as bone are complex and no doubt multifactorial. Members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) family, particularly bone sialoprotein (BSP) and osteopontin (OPN), exhibit multiple activities known to promote malignant cell proliferation, detachment, invasion, and metastasis of several osteotropic cancers. The expression level of BSP and OPN is elevated in a variety of human cancers, particularly those that metastasize preferentially to the skeleton. Recent studies suggest that the "osteomimicry" of malignant cells is not only conferred by transmembrane receptors bound by BSP and OPN, but includes the "switch" in gene expression repertoire typically expressed in cells of skeletal lineage. Understanding the role of BSP and OPN in tumor progression, altered pathophysiology of bone microenvironment, and tumor metastasis to bone will likely result in development of better diagnostic approaches and therapeutic regimens for osteotropic malignant diseases.
恶性细胞转移到骨等继发性部位的机制很复杂，毫无疑问是多因素的。小整合素结合配体 N-连接糖蛋白（SIBLINGs）家族的成员，特别是骨唾液蛋白（BSP）和骨桥蛋白（OPN），具有多种已知的促进恶性细胞增殖、分离、侵袭和转移的活性，几种亲骨性癌症。BSP 和 OPN 的表达水平在多种人类癌症中升高，特别是那些优先转移到骨骼的癌症。最近的研究表明，恶性细胞的“类骨质模拟”不仅由 BSP 和 OPN 结合的跨膜受体赋予，还包括通常在骨骼谱系细胞中表达的基因表达谱的“开关”。了解 BSP 和 OPN 在肿瘤进展、骨微环境病理生理学改变以及肿瘤转移到骨中的作用，可能会导致开发出更好的亲骨性恶性疾病的诊断方法和治疗方案。
