Elevated level of inhibin-alpha subunit is pro-tumourigenic and pro-metastatic and associated with extracapsular spread in advanced prostate cancer.
Elevated level of inhibin-alpha subunit is pro-tumourigenic and pro-metastatic and associated with extracapsular spread in advanced prostate cancer.
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DOI：
10.1038/sj.bjc.6605089
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发表时间：
2009-06-02
影响因子：
8.8
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中科院分区：
文献类型：
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前列腺素α亚基（INHα）在前列腺癌（PCa）中的生物学功能目前尚不清楚。最近的一项研究表明，PCa患者INHα水平升高与复发风险较高有关。这促使我们使用临床标本和功能研究来研究INHα的促肿瘤发生和促转移功能。我们进行了一项横断面研究，以确定INHα表达与许多临床病理学参数之间的联系，这些参数包括Gleason评分、手术切缘、囊外扩散、淋巴结状态和血管内皮生长因子受体-3表达，这些都是PCa的公认预后因素。此外，我们还利用两种分别代表雄激素依赖型和非依赖型前列腺癌的人前列腺癌细胞系（LNCaP和PC 3），研究了INHα水平升高在晚期癌症中的生物学功能。原发性PCa组织中INHα表达升高表明PCa患者上述临床病理参数阳性的风险较高。在LNCaP和PC 3细胞中过表达INHα表现出两种不同的细胞类型特异性反应。INHα阳性LNCaP显示肿瘤生长减少，而INHα阳性PC 3细胞显示肿瘤生长增加，并通过淋巴管生成过程转移。本研究首次证明了INHα的促肿瘤发生和促转移功能与雄激素非依赖性转移性前列腺疾病阶段相关。我们的研究结果还表明，INHα在原发性前列腺肿瘤中的表达可以作为PCa预后的预测因素。
The biological function of inhibin-α subunit (INHα) in prostate cancer (PCa) is currently unclear. A recent study associated elevated levels of INHα in PCa patients with a higher risk of recurrence. This prompted us to use clinical specimens and functional studies to investigate the pro-tumourigenic and pro-metastatic function of INHα. We conducted a cross-sectional study to determine a link between INHα expression and a number of clinicopathological parameters including Gleason score, surgical margin, extracapsular spread, lymph node status and vascular endothelial growth factor receptor-3 expression, which are well-established prognostic factors of PCa. In addition, using two human PCa cell lines (LNCaP and PC3) representing androgen-dependent and -independent PCa respectively, we investigated the biological function of elevated levels of INHα in advanced cancer. Elevated expression of INHα in primary PCa tissues showed a higher risk of PCa patients being positive for clinicopathological parameters outlined above. Over-expressing INHα in LNCaP and PC3 cells demonstrated two different and cell-type-specific responses. INHα-positive LNCaP demonstrated reduced tumour growth whereas INHα-positive PC3 cells demonstrated increased tumour growth and metastasis through the process of lymphangiogenesis. This study is the first to demonstrate a pro-tumourigenic and pro-metastatic function for INHα associated with androgen-independent stage of metastatic prostate disease. Our results also suggest that INHα expression in the primary prostate tumour can be used as a predictive factor for prognosis of PCa.