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

Amaç: Artan miktardaki kanıt prostat kanser (PCa) hücrelerinin voltaj kapılı sodyum kanalları (VGSCs)’na sahipolduğunu 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 vit-ro olarak gözlemlenen VGSC ekspresyonunun, bu hücre- lerin sıçanlara subkuten enjekte edildiğinde primer tümör oluştuğunda ve hücreler akciğerlere metastaz yaptığındakorunup 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 des- teklemektedir.

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

Objective: Increasing evidence indicates that prostatecancer (PCa) cells possess voltage-gated sodium chan-nels (VGSCs) and these channels contribute to the meta- static progression of the disease. In the present study, itwas aimed to investigate the heterotopic expression ofVGSCs in carcinogenesis and metastasis. It was evaluat-ed whether the expression of VGSC in strongly metastaticrat Mat-LyLu PCa cells observed in vitro is also conservedwhen these cells form primary tumors and metastasize tothe 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 immuno- chemical techniques. Results: Reverse transcription PCR and immunohisto- chemistry 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.

___

  • 1. Fitzpatrick JM, Schulman C, Zlotta AR, Schröder FH. Prostate cancer: a serious disease suitable for pre- vention. BJU Int T 2009;103:864-870.
  • 2. Grimes JA, Fraser SP, Stephens GJ, et al. Differen- tial expression of voltage-activied Na+ currents in two prostatic tomour cell lines: contribution to invasive- ness in vitro. FEBS Letters 1995;369:290-294.
  • 3. Laniado ME, Lalani EN, Fraser SP, et al. Expression and functional analysis of voltage-activated Na+ channels in human prostate cancer cell lines and their contrubition to invasion in vitro. Am J Pathol 1997;150:1213-1221.
  • 4. Diss JK, Archer SN, Hirano J, et al. Expression pro- files voltage gated Na+ channel alpha-subunit genes in rat and human prostate cancer cell lines. Prostate 2001;48:165-178.
  • 5. Nakajima T, Kubota N, Tsutsumi T, et al. Eicosapentae- noic acid inhibits voltage-gated sodium channels and invasiveness in prostate cancer cells. Br J Pharmacol 2009;156:420-431.
  • 6. Abdul M, Hoosein N. Voltage-gated sodium ion chan- nels in prostate cancer: expression and activity. Anti- cancer Research 2002;22:1727-1730.
  • 7. Diss JK, Stewart D, Pani F, et al. A potential novel marker for human prostate cancer: Voltage-gated so- dium channel expression in vivo. Prostate Cancer & Prostatic Diseases 2005;8:266-273.
  • 8. Roger S, Besson P, Guennec J. Involvement of a novel fast inward sodium current in the invasion capacity of a breast cancer cell line. Biochimica et Biophysica Acta 2003;1616:107-111.
  • 9. Fraser SP, Diss JKJ, Chioni A-M, et al. Voltage-gated sodium channel expression and potentiation of hu- man breast cancer metastasis. Clinical Cancer Re- search 2005;11:5381-5389.
  • 10. Onganer PU, Djamgoz MBA. Small-cell lung cancer (human): Potentiation of endocytic membrane activ- ity by voltage gated Na+ channel expression in vitro. Journal of Membrane Biology 2005;204:67-75.
  • 11. Roger S, Rollin J, Barascu A, et al. Voltage-gated sodium channels potentiate the invasive capaci- ties of human non-small-cell lung cancer cell lines. International Journal of Biochemistry & Cell Biology 2007;39:774-786.
  • 12. Allen DH, Lepple-Wienhues A, Cahalan MD. Ion chan- nel phenotype of melanoma cell lines. J Membrane Biol 1997;155:27-34.
  • 13. Schrey M, Codina C, Kraft R, et al. Molecular charac- terization of voltage-gated sodium channels in human gliomas. Neuroreport 2002;20;13:2493-2498.
  • 14. Fulgenzi G, Graciotti L, Faronato M, et al. Human neoplastic mesothelial cells express voltage-gated sodium channels involved in cell motility. The In- ternational Journal of Biochemistry & Cell Biology 2006;38:1146-1159.
  • 15. Gao R, Shen Y, Cai J, et al. Expression of voltage-gat- ed sodium channel subunit in human ovarian cancer. Oncology Reports 2010;23:1293-1299.
  • 16. House CD, Vaske CD, Schwartz AM, et al. Voltage- gated Na+ channel SCN5A is a key regulator of a gene transcriptional network that controls colon can- cer inavasion. Cancer Res 2010;70:6957-6967.
  • 17. Hernandez-Plata E, Ortiz CS, Marquina-Castillo B, et al. Over expression of Nav1.6 channels is associated with the invasion capacity of human cervical cancer. Inter J Cancer 2011;Doi:10.1002/ijc.26210.
  • 18. Bennett ES, Smith BA, Harper JM. Voltage-gated Na+ channels confer invasive properties on human prostate cancer cells. Pflugers Arch – Eur Physiol 2004;447:908-914.
  • 19. Gillet L, Roger S, Besson P, et al. Voltage-gated so- dium channel activity promotes cysteine cathepsin- dependent invasiveness and colony growth of human cancer cells. J. Biol. Chem 2009;284:8680–8691.
  • 20. Djamgoz MBA, Mycielska M, Madeja Z, et al. Direc- tional movement of rat prostate cancer cells in direct- current electric field: involvement of voltage-gated Na+ channel activity. J Cell Sci 2001;114:2697-2705.
  • 21. Fraser SP, Salvador V, Manning E, et al. Contribution of functional voltage-gated Na+ channel expression to cell behaviours involved in the metastic cascade in rat prostate cancer: I. Lateral motility. J Cell Physiol 2003;169:479-487.
  • 22. Fraser SP, Ding Y, Liu A, et al. Tetrodotoxin sup- presses morphological enhancement of the metastic Mat-LyLu rat prostate cancer cell line. Cell Tissue Res 1999;295:505-512.
  • 23. Krasowska M, Grzywna ZJ, Mycielska ME, Djamgoz MBA. Patterning of endocytotic vesicles and its con- trol by voltage-gated Na+ channel activity in rat pros- tate cancer cells: fractal analyses. Eur Biophys J 2004;33:535–542.
  • 24. Palmer CP, Mycielska ME, Burcu H, et al. Single cell adhesion measuring apparatus (SCAMA): application to cancer cell lines of different metastatic potential and voltage-gated Na+ channel expression. Eur Biophys- ics J 2008;37:359-368.
  • 25. Brackenbury W, Djamgoz MBA. Activity-dependent regulation of voltage-gated Na+ channel expression in Mat-LyLu rat prostate cancer cell line. J Physiology 2006;573:343-356.
  • 26. Brackenbury WJ, Chioni AM, Diss JKJ, Djamgoz MBA. The neonatal splice variant of Nav1.5 potenti- ates in vitro metastatic behaviour of MDA-MB-231 human breast cancer cells. Breast Cancer Res Treat 2007;101:149–160.
  • 27. Khanna C, Hunter K. Modelling metastasis in vivo. Carcinogenesis 2005;26:513-523.
  • 28. Yildirim S, Altun S, Gumushan H, et al. Voltage-gated sodium channel activity promotes prostate cancer metastasis in vivo. Cancer Letters 2012;323:58-61.
  • 29. Hollingshead MG. Antitumor efficacy testing in ro- dents. J Natl Cancer Inst 2008;100:1500-1510.
  • 30. Steeg PS, Theodorescu D. Metastasis: a therapeutic target for cancer. Nat Clin Pract Oncol 2008;5:206– 219.
  • 31. Hunter KW, Crawford NP, Alsarraj JJ. Mechanisms of metastasis. Breast Cancer Res 2008;10:1:S2.
  • 32. Nguyen DX, Massague J. Genetic determinants of cancer metastasis. Nature Reviews Genetics 2007;8:341-352.
Journal of Clinical and Experimental Investigations-Cover
  • Başlangıç: 2010
  • Yayıncı: Sağlık Araştırmaları Derneği
Sayıdaki Diğer Makaleler

Yetmiş yedi yaşında kadın hastada primer kutanöz folikül merkezli lenfoma

Göknur KALKAN, Zennure TAKCI, Emel GÜNGÖR, Ayşegül ÜNER, Celile Gülfer AKBAY, Hatice Meral EKŞİOĞLU

Sol ön inen arter tıkanıklığı ve izole inferior derivasyonlarda ST segment yükselmesiyle seyreden akut miyokart infarktüsü olgusu ve literatürün gözden geçirilmesi

Mehmet Zihni BİLİK, Halit ACET, Ferhat ÖZYURTLU, Faruk ERTAŞ

Olfaktör nöroblastoma (esthesioblastoma) radyolojik bulguları

Mehmet BEYAZAL, Cemil GÖYA, Alpaslan YAVUZ, Çağatay ANDİÇ, Aydın BORA

Yaygın kas-iskelet ağrısı olan hastalarda D vitamini eksikliği prevalansı ve risk faktörleri

Seher KARA, Murat ÖZKAYA, Muharrem ÇİDEM, İlhan KARACAN, Hakan SARI

Lineer liken planuslu bir olgu sunumu: Doğru adlandırmanın kullanılması

Göknur KALKAN, Zennure TAKCI, Gülçin Güler ŞİMŞEK

Kas iskelet sistemi yaralanmalarında Türk toplumunun sınıkçı tercihi ve etkileyen faktörler

Mehmet Nuri KONYA, Ahmet ASLAN, Serdar SARGIN, Aziz ATİK, Gökhan MERİÇ

Metastazı nedeniyle teşhis edilen asemptomatik dev renal kitle: Olgu sunumu

Ali BEYTUR, Ali GÜNEŞ, Fatih OĞUZ, Ramazan ALTINTAŞ, Cemal TAŞDEMİR, Serhan ÇİMEN

Solitary rectal diverticulum: A case report

İsmayil YILMAZ, İsmail DEMİRYILMAZ, Kemal PEKER, Mehmet Seyhan KALKAN

İdrar inkontinansı ile birlikte lomber intraspinal sinovyal kist: Olgu sunumu ve literatür incelemesi

Salih HATTAPOĞLU, Yahya TURAN, Kağan KAMAŞAK, Adnan CEVİZ, Cüneyt GÖÇMEZ, Tevfik YILMAZ

Long-term changes in sexual functions following complicated pregnancies and deliveries

Mehmet Sıddık EVSEN, Abdulkadir TURGUT, Serdar BAŞARANOĞLU, Yasin BEZ, Ahmet YALINKAYA, Talip GÜL, Ali ÖZLER, Pınar TAN