Overexpression of semaphorin 3A promotes tumor progression and predicts poor prognosis in hepatocellular carcinoma after curative resection.
Overexpression of semaphorin 3A promotes tumor progression and predicts poor prognosis in hepatocellular carcinoma after curative resection.
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信号蛋白 3A 的过度表达可促进肿瘤进展并预测肝细胞癌根治性切除后的不良预后。
DOI：
10.18632/oncotarget.10104
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发表时间：
2016-08-09
期刊：
影响因子：
--
通讯作者：
Huang XW
中科院分区：
文献类型：
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作者：
Hu ZQ;Zhou SL;Zhou ZJ;Luo CB;Chen EB;Zhan H;Wang PC;Dai Z;Zhou J;Fan J;Huang XW
semaphorins最初被确定为在神经发育过程中作为指导线索的角色。3类信号蛋白参与癌症进展。然而，3类信号蛋白在肝细胞癌（HCC）中的作用尚不清楚。我们检测了具有不同转移潜能的HCC细胞系和癌组织样本中3类信号蛋白的表达水平。结果表明，脑信号蛋白3A的表达在转移细胞系和肿瘤复发患者的样品中上调。细胞功能研究显示，Semaphorin 3A促进HCC细胞增殖、迁移和侵袭。动物研究表明，脑信号蛋白3A过表达促进肿瘤生长和肺转移。脑信号蛋白3A还充当参与体外巨噬细胞直接募集的化学引诱物，并促进体内肿瘤相关巨噬细胞（TAM）浸润。多变量分析显示，脑信号蛋白3A表达单独或与TAM的数量相结合，可以是总生存时间和复发时间的独立预测因子。总体而言，结果表明脑信号蛋白3A增加了TAM浸润并促进了HCC进展。Semaphorin 3A表达单独或与TAM数量结合，是一个新的预后因素和治疗HCC的潜在靶点。
The semaphorins were originally identified as having roles as guidance cues during neural development. Class 3 semaphorins are involved in cancer progression. However, the roles of class 3 semaphorins in hepatocellular carcinoma (HCC) are unknown. We examined the expression levels of class 3 semaphorins in HCC cell lines with different metastatic potential and in carcinoma tissue samples. The results indicated that Semaphorin 3A expression was up-regulated in metastatic cell lines and in samples from patients with tumor recurrence. Cell functional studies revealed that Semaphorin 3A promoted HCC cell proliferation, migration, and invasion. Animal studies indicated that Semaphorin 3A overexpression enhanced tumor growth and lung metastasis. Semaphorin 3A also acted as a chemoattractant involved in direct recruitment of macrophages in vitro, and facilitated tumor-associated macrophage (TAM) infiltration in vivo. Multivariate analysis revealed that Semaphorin 3A expression alone, or combined with the number of TAMs, can be an independent predictor for overall survival time and time to recurrence. Overall, the results suggested that Semaphorin 3A increased TAM infiltration and promoted HCC progression. Semaphorin 3A expression alone, or combined with the number of TAMs, is a new prognostic factor and potential target for the treatment of HCC.