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Carcinogenesis, Vol. 21, No. 2, 325-330, February 2000
© 2000 Oxford University Press

Short Communications

Altered surface expression and increased turnover of the {alpha}6ß4 integrin in an undifferentiated carcinoma

Colette M. Witkowski2, G.Tim Bowden, Ray B. Nagle1 and Anne E. Cress3

Department of Radiation Oncology and
1 Department of Pathology, The University of Arizona Cancer Center, 1515 North Campbell Avenue, Tucson, AZ 85724-5024, USA
2 Present address: Biomedical Sciences Department, Southwest Missouri State University, 901 South National Avenue, Springfield, MO 65804-0094, USA

The integrin {alpha}6ß4, predominantly expressed on tissues of epithelial origin, is known to be variably expressed on carcinomas. The biochemical changes resulting in altered expression during tumor progression are unknown. We have analyzed the expression of {alpha}6ß4 in a multi-step mouse model of skin carcinogenesis representing normal keratinocyte, benign papilloma and malignant undifferentiated carcinoma. All cell lines expressed the {alpha}6 integrin exclusively as the {alpha}6ß4 integrin heterodimer. Analysis of this integrin by flow cytometry and immunoprecipitation of surface labeled proteins revealed that the undifferentiated carcinoma cells have an ~75% reduction in surface expression of the integrin as compared with the keratinocyte and papilloma cell lines. The {alpha}6ß4 integrin which remains expressed on the carcinoma cells is diffusely distributed in the membrane and has an ~2.5-fold increased biological turnover as compared with normal keratinocytes. The decreased biological half-life and the loss of polarized expression of {alpha}6ß4 on the carcinoma cells suggests an altered functional role for the {alpha}6ß4 integrin on carcinoma cells during tumor progression. These factors may contribute to the known supression of hemidesmosome structures and the increased migration phenotype associated with some epithelial carcinomas.

Abbreviations: DPBS, Dulbecco's phosphate-buffered saline; ECM, extracellular matrix.


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