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Breast cancer invasion is mediated by beta-N-acetylglucosaminidase (beta-NAG) and associated with a dysregulation in the secretory pathway of cancer cells

Ramessur, K.T. and Greenwell, Pamela and Nash, R. and Dwek, Miriam (2010) Breast cancer invasion is mediated by beta-N-acetylglucosaminidase (beta-NAG) and associated with a dysregulation in the secretory pathway of cancer cells. British Journal of Biomedical Science, 67 (4). pp. 189-196. ISSN 0967-4845

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Official URL: http://www.bjbs-online.org/article.asp?id=436

Abstract

The extracellular matrix is enriched with carbohydrate polymers that mask the protein backbone. This study aims to test the hypothesis that for successful cancer cell invasion the cells must secrete glycosidases to reveal the protein backbone, and then the action of proteases provides the physical space needed for cancer cell movement. Thus, the activity of intracellular and secreted beta-N-acetylglucosaminidase (beta-NAG) was assayed in luminal breast epithelial cells (HB4a) and breast cancer cells (BT474, ZR75-1, MDA-MB-435, MCF7). An increase in the V(max) of beta-NAG was observed in MDA-MB-435 and MCF7 cells. Exoglycosidases are normally located in the lysosomes and function at an acidic pH, but in the cancer cells there was significant enzyme activity at neutral pH. A change in lysosome location and number was observed in the cancer cells, consistent with alterations in the secretory pathway. Finally, applying a cocktail of protease inhibitors resulted in a 20% reduction in invasion of MDA-MB-435 cells through Matrigel after 24 h, and when the cells were treated with protease and beta-NAG inhibitors then cellular invasion was reduced by > 60%. The results suggest combination therapies that inhibit proteases and glycosidases might be a rational way forward for the design of drugs aimed at arresting cellular invasion.

Item Type:Article
Research Community:University of Westminster > Life Sciences, School of
ID Code:9105
Deposited On:10 Feb 2011 15:55
Last Modified:10 Feb 2011 15:55

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