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Transition from the Noninvasive to the Invasive Phenotype and Loss of -Catenin in Human Colon Cancer Cells¹

Department of Radiotherapy, Nuclear Medicine and Experimental Cancerology, University Hospital, De Pintelaan 185 [S. J. V., E. A. B., M. E. B., G. K. D. B., K. M. V., M. M. M.], and Laboratory of Molecular Biology, Section of Molecular Cell Biology, University of Ghent, Ledeganckstraat 35 [K. L., V., G. J. B., F. M. v. R.], B-9000 Ghent, Belgium

Loss of epithelioid organization in carcinoma cell lines has been related to invasiveness and poor differentiation of tumors. We investigated the invasion in vitro of various human colon cancer cell lines. Most cell lines were noninvasive into chick heart fragments, and this correlated with an epithelioid morphotype. Only cell lines COLO320DM, SW620, and variants of HCT-8 and DLD-1 were invasive and nonepithelioid. We examined in these cell lines whether invasiveness was related to changes in the structure and function of the E-cadherin/catenin complex. E-cadherin functions as an invasion suppressor and as a cell-cell adhesion molecule when linked to the cytoskeleton via -catenin plus ß- or -catenin. All noninvasive cell lines showed E-cadherin linked to these catenins. The E-cadherin-dependent cell-cell adhesion function in these cell lines was demonstrated by two assays in vitro. It was interesting that all invasive cell lines showed a dysfunctional E-cadherin/catenin complex. COLO320DM, SW480, and SW620 cells were defective in E-cadherin expression, whereas the invasive variants of HCT-8 and DLD-1 lacked the -catenin protein. From clonal epithelioid HCT-8 cultures with functional E-cadherin/catenin complexes, we subcloned, repeatedly, round cell variants that were again invasive and expressed no -catenin protein. Our data suggest that reproducible transformations toward a more invasive phenotype in HCT-8 cells are associated with down-regulation of -catenin. The mechanisms of this transformation and the level of -catenin down-regulation are currently investigated.

¹ Supported by the National Fonds voor Wetenschappelijk Onderzoek, the Vereniging voor Kankerbestrijding VZW, the Sportvereniging tegen Kanker, the Effel Schenking, the ASLK/VIVA-verzekeringen, and the G.O.A. van de Vlaamse Gemeenschap, Brussels, Belgium.

² To whom requests for reprints should be addressed.

Received 6/ 1/95. Accepted 8/14/95.

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