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Journal of Cell Science 114, 2697-2705 (2001)
© 2001 The Company of Biologists Limited

RESEARCH ARTICLE

Directional movement of rat prostate cancer cells in direct-current electric field

involvement of voltagegated Na+ channel activity

Mustafa B. A. Djamgoz1,*, Maria Mycielska1,2, Zbigniew Madeja2, Scott P. Fraser1 and Wlodzimierz Korohoda2

1 Department of Biology, Imperial College of Science, Technology and Medicine, Sir Alexander Fleming Building, London, SW7 2AZ, UK
2 Department of Cell Biology, Institute of Molecular Biology, Jagiellonian University, 31-120 Krakow, Poland
* Author for correspondence (e-mail: m.djamgoz{at}ic.ac.uk )

Accepted April 12, 2001

A two-part hypothesis has been tested, which proposes that (1) prostate cancer cells are galvanotactic (i.e. respond to an electric field by moving directionally) and (2) voltagegated Na+ channel activity, which was shown previously to be expressed specifically by strongly metastatic cells, controls galvanotaxis. Two well-defined rat (`Dunning') cell lines, originally derived from the same prostate tumour but differing markedly in their metastatic ability, were used. Cells were exposed to exogenous direct-current electric fields of physiological strength (0.1-4.0 V cm-1), their reactions were recorded by light microscopy and analysed by a quantitative tracking method. Voltage-gated Na+ channel activity was modulated pharmacologically using a range of concentrations of a specific channel blocker (tetrodotoxin) or an opener (veratridine). The results showed that the highly metastatic MAT-LyLu cells responded to the application of the electric field strongly by migrating towards the cathode. By contrast, the weakly metastatic At-2 cells gave no such response. Tetrodotoxin suppressed the galvanotactic response of the MAT-LyLu cells whereas veratridine enhanced it. Both compounds had little effect on the AT-2 cells. These results are consistent with functional voltage-gated Na+ channel expression occurring specifically in highly metastatic cells. This is also the first demonstration of control of galvanotaxis, in any cell type, by voltage-gated Na+ channel activity. The possible underlying mechanisms and the in vivo relevance of these findings are discussed.

Key words: Cancer, Metastasis, Voltage-gated Na+ channel, Prostate, Dunning, Rat






© The Company of Biologists Ltd 2001