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Molecular Cell Biology Unit, Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology, University of Gent, B-9000 Gent, Belgium [A. K., S. B., P. V., F. v. R.]; Department of Experimental Cancerology, University Hospital Gent, B-9000 Gent, Belgium [E. B., M. M.]; and Department of Molecular Cancer Biology, Danish Cancer Society, DK-2100 Copenhagen, Denmark [E. L.]
Metastasin is putatively associated with cytoskeletal proteins and may influence cell motility, although its exact physiological role is not known. Because E-cadherin is an invasion suppressor molecule, and metastasin a metastasis-inducing molecule, we wondered which molecule was playing a dominant role in the balance that finally leads to noninvasiveness or invasiveness. The expression levels of E-cadherin and metastasin were monitored in two mouse tumor cell families and were found to be inversely regulated. Moreover, overexpression obtained via transfection of plasmids coding for either one of these two molecules abrogated expression of the other molecule as investigated via Northern and Western blotting experiments. Invasiveness was accordingly influenced. Expression levels of
- and ß-catenins were not influenced by up-regulated metastasin, but their intracellular distribution was disturbed. The present results suggest that metastasin-induced invasiveness of several malignant tumor cells is at least partially caused by down-regulation of E-cadherin.
1 This work was supported by the Vlaams Instituut voor de Bevordering van het Wetenschappelijk-Technologisch Onderzoek in de Industrie, the Vlaamse Kankerliga, the Belgian Cancer Association, the Sportvereniging tegen Kanker, ASLK-verzekeringen, the Centrum voor Studie en Behandeling van Gezwelziekten, Belgium, and the Danish Medical Research Council.
2 To whom requests for reprints should be addressed, at the Molecular Cell Biology Unit, Department of Molecular Biology, V.I.B.University of Gent, Ledeganckstraat 35, B-9000 Gent, Belgium. Phone: 32-9-264-5017; Fax: 32-9-264-5331; E-mail: F.VANROY@DMB.RUG.AC.BE.
Received 7/ 3/98. Accepted 9/ 1/98.
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