Expression of voltage-gated sodium channel in primary tumors and corresponding metastases in the Copenhagen rat model of prostate cancer

Abstract

Objective: Increasing evidence indicates that prostate cancer (PCa) cells possess voltage-gated sodium channels (VGSCs) and these channels contribute to the metastatic progression of the disease. In the present study, it was aimed to investigate the heterotopic expression of VGSCs in carcinogenesis and metastasis. It was evaluated whether the expression of VGSC in strongly metastatic rat Mat-LyLu PCa cells observed in vitro is also conserved when these cells form primary tumors and metastasize to the lungs upon their subcutaneous injection in rats. Methods: PCa model was induced in male Copenhagen rats by subcutaneous implantation of strongly metastatic Mat-LyLu cells. The expression of VGSCs was studied in the model utilizing molecular biological and immunochemical techniques. Results: Reverse transcription PCR and immunohistochemistry showed that the expression of VGSC is conserved in the primary prostate tumors of Mat-LyLu and not eliminated in the corresponding lung metastases at both the mRNA and protein level. Conclusion: The results are consistent with the predominant role of VGSC in the metastatic progression of PCa and consistently support the VGSC hypothesis of cancer progression. J Clin Exp Invest 2013; 4 (4): 422-428

Keywords

• Prostate cancer, voltage-gated sodium channel, primary tumor, metastasis

Prostat kanseri Copenhagen sıçan modelinin primer tümörleri ve metastazlarında voltaj kapılı sodyum kanal ekspresyonu

Öz

Amaç: Artan miktardaki kanıt prostat kanser (PCa) hücrelerinin voltaj kapılı sodyum kanalları (VGSCs)\'na sahip olduğunu ve bu kanalların hastalığın metastatik ilerlemesine katkıda bulunduğunu göstermektedir. Mevcut çalışmada, VGSC\'lerin karsigonezde ve metastazdaki heterotopik ekspresyonunu araştırmak amaçlanmıştır. Güçlü metastatik sıçan Mat-LyLu PCa hücrelerinde in vitro olarak gözlemlenen VGSC ekspresyonunun, bu hücrelerin sıçanlara subkuten enjekte edildiğinde primer tümör oluştuğunda ve hücreler akciğerlere metastaz yaptığında korunup korunmadığı, değerlendirilmiştir. Yöntemler: PCa modeli Copenhagen ırkı erkek sıçanlarda güçlü metastatik Mat-LyLu hücrelerinin subkuten implantasyonu ile oluşturulmuştur. VGSC eksprsyonu bu modelde moleküler biyolojik ve immünokimyasal yöntemlerle araştırılmıştır. Bulgular: Ters transkripsiyon PCR ve immünohistokimya yöntemleri VGSC ekspresyonunun Mat-LyLu primer prostat tümörlerinde korunduğunu ve akciğer metatsazlarında da bu ekspresyonun devam ettiğini, mRNA ve protein düzeyinde göstermiştir. Sonuç: Sonuçlar, VGSC\'lerin PCa\'nin metastatik ilerlemesindeki baskın rolü ile uyumludur ve ‘kanserin ilerlemesinde VGSC\'lerin rolü\' hipotezini tutarlı bir şekilde desteklemektedir.

Anahtar Kelimeler

• Prostat kanseri, voltaj-kapılı sodyum kanalı, primer tümör, metastaz

Kaynakça

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