The Role of Semaphorin 4D in Bone Remodeling and Cancer Metastasis.
The Role of Semaphorin 4D in Bone Remodeling and Cancer Metastasis.
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DOI：
10.3389/fendo.2018.00322
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发表时间：
2018
影响因子：
5.2
通讯作者：
Suvannasankha A
中科院分区：
文献类型：
--
作者：
Lontos K;Adamik J;Tsagianni A;Galson DL;Chirgwin JM;Suvannasankha A
Semaphorin 4D （Sema4D; CD100）是Semaphorin家族的一种150 kda的跨膜二聚体糖蛋白。信号蛋白最初被确定为引导神经轴突生长的化学再生剂。Sema4D还具有免疫调节活性。最近的数据表明，Sema4D还具有其他功能：血小板失活、刺激血管生成和调节骨形成。Sema4D是一种在破骨细胞上表达的偶联因子，可抑制成骨细胞分化。因此，阻断Sema4D可能对骨具有合成代谢作用。Sema4D及其受体丛状蛋白b1在癌症中普遍失调，提示在癌症进展、侵袭、肿瘤血管生成和骨骼转移中起作用。本文综述了Sema4D在骨和癌症生物学中的作用及其分子通路，特别是Sema4D- plexin - b1信号串扰在癌细胞和骨髓微环境相关区域，因为人源化的Sema4D中和抗体目前正在癌症和神经系统疾病的早期临床试验中。
Semaphorin 4D (Sema4D; CD100) is a transmembrane homodimer 150-kDa glycoprotein member of the Semaphorin family. Semaphorins were first identified as chemorepellants that guide neural axon growth. Sema4D also possesses immune regulatory activity. Recent data suggest other Sema4D functions: inactivation of platelets, stimulation of angiogenesis, and regulation of bone formation. Sema4D is a coupling factor expressed on osteoclasts that inhibits osteoblast differentiation. Blocking Sema4D may, therefore, be anabolic for bone. Sema4D and its receptor Plexin-B1 are commonly dysregulated in cancers, suggesting roles in cancer progression, invasion, tumor angiogenesis, and skeletal metastasis. This review focuses on Sema4D in bone and cancer biology and the molecular pathways involved, particularly Sema4D–Plexin-B1 signaling crosstalk between cancer cells and the bone marrow microenvironment—pertinent areas since a humanized Sema4D-neutralizing antibody is now in early phase clinical trials in cancers and neurological disorders.