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Loss of Epithelial Markers and Acquisition of Vimentin Expression in Adriamycin- and Vinblastine-resistant Human Breast Cancer Cell Lines¹

Lombardi Cancer Research Center [C. L. S., S. E. H., J. M. S., P. W., J. A. T., E. W. T., S. W. B., E. P. G.], and Departments of Anatomy and Cell Biology [C. L. S., E. W. T., S. W. B., E. P. G.] and Medicine [C. L. S., J. M. S., E. P. G.], Division of Medical Oncology, Georgetown University, Washington, DC 20007

We have previously observed that breast cancer cell lines could exhibit either epithelial or fibroblastic phenotypes as reflected by their morphologies and intermediate filament protein expression (C. L. Sommers, D. Walker-Jones, S. E. Heckford, P. Worland, E. Valverius, R. Clark, M. Stampfer, and E. P. Gelmann, Cancer Res., 49: 4258–4263, 1989). Fibroblastoid, vimentin-expressing breast cancer cell lines are more invasive in vitro and in vivo (E. W. Thompson, S. Paik, N. Brunner, C. L. Sommers, G. Zugmaier, R. Clarke, T. B. Shima, J. Torri, S. Donahue, M. E. Lippman, G. R. Martin, and R. B. Dickson, J. Cell. Physiol., 150: 534–544, 1992). We hypothesized that a breast cancer cell with an epithelial phenotype could undergo a transition to a fibroblastic phenotype, possibly resulting in more invasive capacity. We now show that two Adriamycin-resistant MCF-7 cell lines and a vinblastine-resistant ZR-75-B cell line have undergone such a transition. Adriamycin-resistant MCF-7 cells express vimentin, have diminished keratin 19 expression, have lost cell adhesion molecule uvomorulin expression, and have reduced formation of desmosomes and tight junctions as determined by reduced immunodetection of their components desmoplakins I and II and zonula occludens (ZO)-1. Other MCF-7 cell lines selected for resistance to vinblastine and to Adriamycin and verapamil did not have these characteristics, indicating that drug selection does not invariably cause these phenotypic changes. In addition, to determine if vimentin expression in MCF-7 cells alone could manifest a fibroblastic phenotype, we transfected the full-length human vimentin complementary DNA into MCF-7 cells. Although vimentin expression was achieved in MCF-7 cells, it did not affect the phenotype of the cells in terms of the distribution of keratins, desmoplakins I and II, ZO-1, or uvomorulin or in terms of in vitro invasiveness. We conclude that vimentin expression is a marker for a fibroblastic and invasive phenotype in breast cancer cells but does not by itself give rise to this phenotype.

¹ This work was supported by developmental funds from the Lombardi Cancer Research Center.

² Present address: Department of Pathology, Flinders Medical Centre, Bedford Park, South Australia 5042.

³ To whom requests for reprints should be addressed, at Division of Medical Oncology, Georgetown University Medical Center, 3800 Reservoir Road NW, Washington, DC 20007-2197.

Received 10/16/91. Accepted 7/27/92.

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