3 类信号素在前列腺癌中的作用。

A role for class 3 semaphorins in prostate cancer.

机构信息

Prostate Cancer Research Center, UCL London, UK.

出版信息

Prostate. 2011 May;71(6):649-58. doi: 10.1002/pros.21281. Epub 2010 Oct 14.

DOI:10.1002/pros.21281

PMID:20949546

Abstract

BACKGROUND

Class 3 semaphorins are secreted proteins that act as guidance cues for migrating cells via their transmembrane receptors plexins and neuropilins. Semaphorins have a role in cancer affecting tumor progression both directly, and indirectly by affecting angiogenesis.

METHODS

The expression of semaphorins and their receptors in prostate cancer cell lines and tissue was determined by RT-PCR, Western blotting and immunohistochemistry. The effect of Sema3E on prostate cancer cell lines was determined by adhesion assays and transwell migration assays.

RESULTS

Semaphorins and their receptors, plexins and neuropilins, are widely co-expressed in prostate cancer cell lines and tissue with a significant overexpression of Sema3E in tumor tissue. Sema3E affected integrin-mediated adhesion to fibronectin of prostate cancer cells, and inhibited their motility. Expression of Sema3C was upregulated and Sema3A and Sema3E were down regulated in prostate cells by hypoxia, consistent with an additional role for Sema3A and 3E as anti-angiogenic factors in prostate cancer.

CONCLUSIONS

Semaphorin 3E is aberrantly expressed in prostate cancer and affects adhesion and motility of prostate cancer cells, indicating a role for the Sema3E/PlexinD1 signaling pathway in prostate cancer and identifying a new possible target for therapy.

摘要

背景

III 类信号素是分泌蛋白，通过其跨膜受体丛蛋白和神经纤毛蛋白，作为迁移细胞的导向线索。信号素在癌症中发挥作用，直接影响肿瘤进展，间接影响血管生成。

方法

通过 RT-PCR、Western blot 和免疫组织化学测定前列腺癌细胞系和组织中信号素及其受体的表达。通过黏附实验和 Transwell 迁移实验测定 Sema3E 对前列腺癌细胞系的影响。

结果

信号素及其受体丛蛋白和神经纤毛蛋白在前列腺癌细胞系和组织中广泛共表达，肿瘤组织中 Sema3E 表达显著上调。Sema3E 影响前列腺癌细胞对纤维连接蛋白的整合素介导黏附，并抑制其迁移。缺氧使前列腺细胞中 Sema3C 的表达上调，Sema3A 和 Sema3E 的表达下调，表明 Sema3A 和 Sema3E 作为前列腺癌中的抗血管生成因子具有额外作用。