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Molecular Cancer
Published in: Molecular Cancer 1/2007

Open Access 01-12-2007 | Research

Epidermal growth factor potentiates in vitro metastatic behaviour of human prostate cancer PC-3M cells: involvement of voltage-gated sodium channel

Authors: Pinar Uysal-Onganer, Mustafa BA Djamgoz

Published in: Molecular Cancer | Issue 1/2007

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Abstract

Background

Although a high level of functional voltage-gated sodium channel (VGSC) expression has been found in strongly metastatic human and rat prostate cancer (PCa) cells, the mechanism(s) responsible for the upregulation is unknown. The concentration of epidermal growth factor (EGF), a modulator of ion channels, in the body is highest in prostatic fluid. Thus, EGF could be involved in the VGSC upregulation in PCa. The effects of EGF on VGSC expression in the highly metastatic human PCa PC-3M cell line, which was shown previously to express both functional VGSCs and EGF receptors, were investigated. A quantitative approach, from gene level to cell behaviour, was used. mRNA levels were determined by real-time PCR. Protein expression was studied by Western blots and immunocytochemistry and digital image analysis. Functional assays involved measurements of transverse migration, endocytic membrane activity and Matrigel invasion.

Results

Exogenous EGF enhanced the cells' in vitro metastatic behaviours (migration, endocytosis and invasion). Endogenous EGF had a similar involvement. EGF increased VGSC Nav1.7 (predominant isoform in PCa) mRNA and protein expressions. Co-application of the highly specific VGSC blocker tetrodotoxin (TTX) suppressed the effect of EGF on all three metastatic cell behaviours studied.

Conclusion

1) EGF has a major involvement in the upregulation of functional VGSC expression in human PCa PC-3M cells. (2) VGSC activity has a significant intermediary role in potentiating effect of EGF in human PCa.
Appendix
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Literature
1.
Nomura AM, Kolonel LN: Prostate cancer: a current perspective. Epidemiol Rev. 1991, 13: 200-27.PubMed
2.
Penson DF, Albertsen PC: Lessons learnt about early prostate cancer from large scale databases: population-based pearls of wisdom. Surg Oncol. 2002, 11: 3-11. 10.1016/S0960-7404(02)00009-9CrossRefPubMed
3.
Djamgoz MBA: Voltage-gated sodium channel activity and metastasis: A novel approach to understanding the pathophysiology of prostate cancer. J Physiol. 1998, 513P: 21-22.
4.
Grimes JA, Fraser SP, Laniado ME, Foster CS, Abel PD, Djamgoz MBA: Differential expression of voltage-activated Na+ currents in two prostatic tumour cell lines: contribution to invasiveness in vitro. FEBS Lett. 1995, 369: 290-294. 10.1016/0014-5793(95)00772-2CrossRefPubMed
5.
Laniado ME, Lalani EN, Fraser SP, Grimes JA, Bhangal G, Djamgoz MB, Abel PD: Expression and functional analysis of voltage-activated Na+ channels in human prostate cancer cell lines and their contribution to invasion in vitro. Am J Pathol. 1997, 150: 1213-21.PubMedCentralPubMed
6.
Fraser SP, Ding Y, Liu A, Foster CS, Djamgoz MBA: Tetrodotoxin suppresses morphological enhancement of the metastatic MAT-LyLu rat prostate cancer cell line. Cell Tissue Res. 1999, 295: 505-512. 10.1007/s004410051256CrossRefPubMed
7.
Djamgoz MBA, Mycielska ME, Madeja Z, Fraser SP, Korohoda W: Directional 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.PubMed
8.
Mycielska M, Fraser SP, Szatkowski M, Djamgoz MBA: Contribution of functional voltage-gated Na+ channel expression to cell behaviours involved in the metastatic cascade in rat prostate cancer. II Secretory membrane activity. J Cell Physiol. 2003, 195: 461-469. 10.1002/jcp.10265CrossRefPubMed
9.
Palmer CP, Mycielska ME, Burcu H, Osman K, Collins T, Beckerman R, Perrett R, Aydar E, Djamgoz MBA: A micro-pressure system for measuring single cell adhesion: application to cancer cell lines of different metastatic potential and voltage-gated Na+ channel expression. Eur Biophys J. 2007, ,
10.
Brackenbury WJ, Djamgoz MB: Activity-dependent regulation of voltage-gated Na+ channel expression in Mat-LyLu rat prostate cancer cell line. J Physiol. 2006, 573: 343-56. 10.1113/jphysiol.2006.106906PubMedCentralCrossRefPubMed
11.
Smith P, Rhodes NP, Shortland AP, Fraser SP, Djamgoz MBA, Ke Y, Foster CS: Sodium channel protein expression enhances the invasiveness of rat and human prostate cancer cells. FEBS Lett. 1998, 423: 19-24. 10.1016/S0014-5793(98)00050-7CrossRefPubMed
12.
Bennett ES, Smith BA, Harper JM: Voltage-gated Na+ channels confer invasive properties on human prostate cancer cells. Pflugers Arch. 2004, 447: 908-914. 10.1007/s00424-003-1205-xCrossRefPubMed
13.
Diss JK, Archer SN, Hirano J, Fraser SP, Djamgoz MBA: Expression profiles of voltage-gated Na+ channel α-subunit genes in rat and human prostate cancer cell lines. Prostate. 2001, 48: 165-178. 10.1002/pros.1095CrossRefPubMed
14.
Diss JK, Stewart D, Pani F, Foster CS, Walker MM, Patel A, Djamgoz MB: A potential novel marker for human prostate cancer: voltage-gated sodium channel expression in vivo. Prostate Cancer Prostatic Dis. 2005, 8: 266-273. 10.1038/sj.pcan.4500796CrossRefPubMed
15.
Lou JY, Laezza F, Gerber BR, Xiao M, Yamada KA, Hartmann H, Craig AM, Nerbonne JM, Ornitz DM: Fibroblast growth factor 14 is an intracellular modulator of voltage-gated sodium channels. J Physiol. 2005, 569: 179-193. 10.1113/jphysiol.2005.097220PubMedCentralCrossRefPubMed
16.
Lei S, Dryden WF, Smith PA: Nerve growth factor regulates sodium but not potassium channel currents in sympathetic B neurons of adult bullfrogs. Neurophysiol. 2001, 86: 641-650.
17.
Toledo-Aral JJ, Brehm P, Halegoua S, Mandel G: A single pulse of nerve growth factor triggers long-term neuronal excitability through sodium channel gene induction. Neuron. 1995, 14: 607-611. 10.1016/0896-6273(95)90317-8CrossRefPubMed
18.
Brackenbury WJ, Djamgoz MB: Nerve growth factor enhances voltage-gated Na channel activity and Transwell migration in Mat-LyLu rat prostate cancer cell line. J Cell Physiol. 2007, 210: 602-608. 10.1002/jcp.20846PubMedCentralCrossRefPubMed
19.
Ding Y, Brackenbury WJ, Onganer PU, Montano X, Porter L, Bates LF, Djamgoz MBA: Epidermal growth factor upregulates motility of Mat-LyLu rat prostate cancer cells partially via voltage-gated sodium channel activity. J Cell Physiol. 2007, [Epub ahead of print],
20.
Culig Z, Hobisch A, Cronauer MV, Radmayr C, Trapman J, Hittmair A, Bartsch G, Klocker H: Androgen receptor activation in prostatic tumor cell lines by insulin-like growth factor-I, keratinocyte growth factor, and epidermal growth factor. Cancer Res. 1996, 54: 5474-5478.
21.
Delongchamps NB, Peyromaure M, Dinh-Xuan AT: Role of vascular endothelial growth factor in prostate cancer. Urology. 2006, 68: 244-248. 10.1016/j.urology.2006.03.010CrossRefPubMed
22.
Hakariya T, Shida Y, Sakai H, Kanetake H, Igawa T: EGFR signaling pathway negatively regulates PSA expression and secretion via the PI3K-Akt pathway in LNCaP prostate cancer cells. Biochem Biophys Res Commun. 2006, 342: 92-100. 10.1016/j.bbrc.2006.01.106CrossRefPubMed
23.
Greene GF, Kitadai Y, Pettaway CA, von Eschenbach AC, Bucana CD, Fidler IJ: Correlation of metastasis-related gene expression with metastatic potential in human prostate carcinoma cells implanted in nude mice using an in situ messenger RNA hybridization technique. Am J Pathol. 1997, 150: 1571-1582.PubMedCentralPubMed
24.
Arora R, Koch MO, Eble JN, Ulbright TM, Li L, Cheng L: Heterogeneity of Gleason grade in multifocal adenocarcinoma of the prostate. Cancer. 2004, 100: 2362-2366. 10.1002/cncr.20243CrossRefPubMed
25.
Roznovanu SL, Amalinci C, Radulescu D: Molecular mechanisms in hormone-resistant prostate cancer. Rev Med Chir Soc Med Nat Iasi. 2005, 109: 577-583.PubMed
26.
Torring N, Jorgensen PE, Poulsen SS, Nexo E: Epidermal growth factor in the rat prostate: production, tissue content and molecular forms in the different prostatic lobes. Prostate. 1998, 35: 35-42. 10.1002/(SICI)1097-0045(19980401)35:1<35::AID-PROS5>3.0.CO;2-GCrossRefPubMed
27.
Gregory J, Willshire IR, Kavanagh JP, Blacklock NJ, Chowdury S, Richards RC: Urogastrone-epidermal growth factor concentrations on prostatic fluid of normal individuals and patients with benign prostatic hypertrophy. Clin Sci. 1986, 70: 359-363.CrossRefPubMed
28.
Bonaccorsi L, Muratori M, Carloni V, Marchiani S, Formigli L, Forti G, Baldi E: The androgen receptor associates with the epidermal growth factor receptor in androgen-sensitive prostate cancer cells. Steroids. 2004, 69: 549-552. 10.1016/j.steroids.2004.05.011CrossRefPubMed
29.
Gann PH, Klein KG, Chatterton RT, Ellman AE, Grayhack JT, Nadler RB, Lee C: Growth factors in expressed prostatic fluid from men with prostate cancer, BPH, and clinically normal prostates. Prostate. 1999, 40: 248-255. 10.1002/(SICI)1097-0045(19990901)40:4<248::AID-PROS6>3.0.CO;2-MCrossRefPubMed
30.
De Miguel P, Royuela , Bethencourt R, Ruiz A, Fraile B, Paniagua R: Immunohistochemical comparative analysis of transforming growth factor alpha, epidermal growth factor, and epidermal growth factor receptor in normal, hyperplastic and neoplastic human prostates. Cytokine. 1999, 11: 722-727. 10.1006/cyto.1998.0443CrossRefPubMed
31.
Hegeman RB, Liu G, Wilding G, McNeel DG: Newer therapies in advanced prostate cancer. Clin Prostate Cancer. 2004, 3: 150-156.CrossRefPubMed
32.
Oda K, Matsuoka Y, Funahashi A, Kitano H: A comprehensive pathway map of epidermal growth factor receptor signaling. Mol Syst Biol. 2005, 1: 2005.0010. 10.1038/msb4100014PubMedCentralCrossRefPubMed
33.
Hilborn MD, Rane SG, Pollock JD: EGF in combination with depolarization or cAMP produces morphological but not physiological differentiation in PC12 cells. J Neurosci Res. 1997, 47: 16-26. 10.1002/(SICI)1097-4547(19970101)47:1<16::AID-JNR2>3.0.CO;2-ICrossRefPubMed
34.
Toral C, Solano-Agama C, Reyes-Marquez B, Sabanero M, Talamas P, Gonzalez Del Pliego M, Mendoza-Garrido ME: Role of extracellular matrix-cell interaction and epidermal growth factor (EGF) on EGF-receptors and actin cytoskeleton arrangement in infantile pituitary cells. Cell Tissue Res. 2007, 327: 143-153. 10.1007/s00441-006-0248-7CrossRefPubMed
35.
Tapia JA, Camello C, Jensen RT, Garcia LJ: EGF stimulates tyrosine phosphorylation of focal adhesion kinase (p125FAK) and paxillin in rat pancreatic acini by a phospholipase C-independent process that depends on phosphatidylinositol 3-kinase, the small GTP-binding protein, p21rho, and the integrity of the actin cytoskeleton. Biochim Biophys Acta. 1999, 1448: 486-499. 10.1016/S0167-4889(98)00157-8CrossRefPubMed
36.
Chan AS, Wong YH: Epidermal growth factor differentially augments G(i)-mediated stimulation of c-Jun N-terminal kinase activity. Br J Pharmacol. 2004, 142: 635-646. 10.1038/sj.bjp.0705851PubMedCentralCrossRefPubMed
37.
Djakiew D, Delsite R, Pflug B, Wrathall J, Lynch JH, Onoda M: Regulation of growth by a nerve growth factor-like protein which modulates paracrine interactions between a neoplastic epithelial cell line and stromal cells of the human prostate. Cancer Res. 1991, 51: 3304-3310.PubMed
38.
Pienta KJ, Isaacs WB, Vindivich D, Coffey DS: The effects of basic fibroblast growth factor and suramin on cell motility and growth of rat prostate cancer cells. J Urol. 1991, 145: 199-202.PubMed
39.
Barrack ER: TGF beta in prostate cancer: a growth inhibitor that can enhance tumorigenicity. Prostate. 1997, 31: 61-70. 10.1002/(SICI)1097-0045(19970401)31:1<61::AID-PROS10>3.0.CO;2-MCrossRefPubMed
40.
Balbay MD, Pettaway CA, Kuniyasu H, Inoue K, Ramirez E, Li E, Fidler IJ, Dinney CP: Highly metastatic human prostate cancer growing within the prostate of athymic mice overexpresses vascular endothelial growth factor. Clin Cancer Res. 1999, 5: 783-789.PubMed
41.
Nishimura K, Kitamura M, Takada S, Nonomura N, Tsujimura A, Matsumiya K, Miki T, Matsumoto K, Okuyama A: Regulation of invasive potential of human prostate cancer cell lines by hepatocyte growth factor. Int J Urol. 1998, 5: 276-281. 10.1111/j.1442-2042.1998.tb00603.xCrossRefPubMed
42.
Rush AM, Wittmack EK, Tyrrell L, Black JA, Dib-Hajj SD, Waxman SG: Differential modulation of sodium channel Na(v)1.6 by two members of the fibroblast growth factor homologous factor 2 subfamily. Eur J Neurosci. 2006, 23: 2551-2562. 10.1111/j.1460-9568.2006.04789.xCrossRefPubMed
43.
Bouron A, Becker C, Porzig H: Functional expression of voltage-gated Na+ and Ca2+ channels during neuronal differentiation of PC12 cells with nerve growth factor or forskolin. Naunyn Schmiedebergs Arch Pharmacol. 1999, 359: 370-377. 10.1007/PL00005363CrossRefPubMed
44.
Lei S, Dryden WF, Smith PA: Nerve growth factor regulates sodium but not potassium channel currents in sympathetic B neurons of adult bullfrogs. J Neurophysiol. 2001, 86: 641-650.PubMed
45.
Kraft R, Basrai D, Benndorf K, Patt S: Serum deprivation and NGF induce and modulate voltage-gated Na currents in human astrocytoma cell lines. Glia. 2001, 34: 59-67. 10.1002/glia.1040CrossRefPubMed
46.
Connolly JM, Rose DP: Production of epidermal growth factor and transforming growth factor-alpha by the androgen-responsive LNCaP human prostate cancer cell line. Prostate. 1990, 16: 209-218. 10.1002/pros.2990160304CrossRefPubMed
47.
Connolly JM, Rose DP: Autocrine regulation of DU145 human prostate cancer cell growth by epidermal growth factor-related polypeptides. Prostate. 1991, 19: 173-180. 10.1002/pros.2990190210CrossRefPubMed
48.
Montano X, Djamgoz MB: Epidermal growth factor, neurotrophins and the metastatic cascade in prostate cancer. FEBS Lett. 2004, 571: 1-8. 10.1016/j.febslet.2004.06.088CrossRefPubMed
49.
Fassett J, Tobolt D, Hansen LK: Type I collagen structure regulates cell morphology and EGF signaling in primary rat hepatocytes through cAMP-dependent protein kinase A. Mol Biol Cell. 2006, 17: 345-356. 10.1091/mbc.E05-09-0871PubMedCentralCrossRefPubMed
50.
Normanno N, De Luca A, Bianco C, Strizzi L, Mancino M, Maiello MR, Carotenuto A, De Feo G, Caponigro F, Salomon DS: Epidermal growth factor receptor (EGFR) signaling in cancer. Gene. 2006, 366: 2-16. 10.1016/j.gene.2005.10.018CrossRefPubMed
51.
Roger S, Potier M, Vandier C, Besson P, Le Guennec JY: Voltage-gated sodium channels: new targets in cancer therapy?. Curr Pharm Des. 2006, 12: 3681-3695. 10.2174/138161206778522047 10.2174/138161206778522047CrossRefPubMed
52.
Anderson JD, Hansen TP, Lenkowski PW, Walls AM, Choudhury IM, Schenck HA, Friehling M, Holl GM, Patel MK, Sikes RA, Brown ML: Voltage-gated sodium channel blockers as cytostatic inhibitors of the androgen-independent prostate cancer cell line PC-3. Mol Cancer Ther. 2003, 2: 1149-1154.PubMed
53.
Zhu XF, Liu ZC, Xie BF, Li ZM, Feng GK, Yang D, Zeng YX: EGFR tyrosine kinase inhibitor AG1478 inhibits cell proliferation and arrests cell cycle in nasopharyngeal carcinoma cells. Cancer Lett. 2001, 169: 27-32. 10.1016/S0304-3835(01)00547-XCrossRefPubMed
54.
Chopra DP, Grignon DJ, Joiakim A, Mathieu PA, Mohamed A, Sakr WA, Powell IJ, Sarkar FH: Differential growth factor responses of epithelial cell cultures derived from normal human prostate, benign prostatic hyperplasia, and primary prostate carcinoma. J Cell Physiol. 1996, 169: 269-280. 10.1002/(SICI)1097-4652(199611)169:2<269::AID-JCP6>3.0.CO;2-MCrossRefPubMed
55.
Jones HE, Eaton CL, Barrow D, Dutkowski CM, Gee JM, Griffiths K: Comparative studies of the mitogenic effects of epidermal growth factor and transforming growth factor-alpha and the expression of various growth factors in neoplastic and non-neoplastic prostatic cell lines. Prostate. 1997, 30: 219-231. 10.1002/(SICI)1097-0045(19970301)30:4<219::AID-PROS1>3.0.CO;2-GCrossRefPubMed
56.
Guo C, Luttrell LM, Price DT: Mitogenic signaling in androgen sensitive and insensitive prostate cancer cell lines. J Urol. 2000, 163: 1027-1032. 10.1016/S0022-5347(05)67876-7CrossRefPubMed
57.
Fraser SP, Diss JK, Chioni AM, Mycielska ME, Pan H, Yamaci RF, Pani F, Siwy Z, Krasowska M, Grzywna Z, Brackenbury WJ, Theodorou D, Koyuturk M, Kaya H, Battaloglu E, De Bella MT, Slade MJ, Tolhurst R, Palmieri C, Jiang J, Latchman DS, Coombes RC, Djamgoz MB: Voltage-gated sodium channel expression and potentiation of human breast cancer metastasis. Clin Cancer Res. 2005, 11: 5381-5389. 10.1158/1078-0432.CCR-05-0327CrossRefPubMed
58.
Onganer PU, Djamgoz MBA: Small-cell lung cancer (human): potentiation of endocytic membrane activity by voltage-gated Na channel expression in vitro. J Membr Biol. 2005, 204: 67-75. 10.1007/s00232-005-0747-6CrossRefPubMed
59.
Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method Methods. 2001, 25: 402-408.
60.
Aydar E, Onganer P, Perrett R, Djamgoz MB, Palmer CP: The expression and functional characterization of sigma (sigma) 1 receptors in breast cancer cell lines. Cancer Lett. 2006, 242: 245-257. 10.1016/j.canlet.2005.11.011CrossRefPubMed
Metadata
Title
Epidermal growth factor potentiates in vitro metastatic behaviour of human prostate cancer PC-3M cells: involvement of voltage-gated sodium channel
Authors
Pinar Uysal-Onganer
Mustafa BA Djamgoz
Publication date
01-12-2007
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2007
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-6-76

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