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BioMed Research International
Volume 2014 (2014), Article ID 804680, 10 pages
http://dx.doi.org/10.1155/2014/804680
Research Article

Invasive Potential of Melanoma Cells Correlates with the Expression of MT1-MMP and Regulated by Modulating Its Association with Motility Receptors via N-Glycosylation on the Receptors

Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Sector 22, Kharghar, Navi Mumbai 410210, India

Received 27 February 2014; Accepted 23 July 2014; Published 11 August 2014

Academic Editor: Ji-Fu Wei

Copyright © 2014 Amit Ranjan and Rajiv D. Kalraiya. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Matrix remodeling and invasion of basement membrane are the major determinants of malignant progression. Matrix degrading enzymes play a pivotal role in this process and have been shown to be regulated at multiple levels. Using high metastatic B16F10 and its invasive variant B16BL6 cells, we previously demonstrated that the expression of β1,6 branched N-oligosaccharides promotes cellular adhesion on different matrix components which in turn induces secretion of MMP9. The present investigations report that although the two cell lines do not differ in the expression of uPAR, expression of MT1-MMP is significantly higher on B16BL6 cells. Analysis of the transcripts of tissue inhibitors of matrix metalloproteinases (TIMPs) showed that expression of both TIMP1 and TIMP2 correlates negatively with the invasive potential of cells. CD44 and β1 integrin, the two important receptors involved in motility, were identified to carry β1,6 branched N-oligosaccharides in an invasive potential dependent manner. However, their glycosylation status did not appear to influence their surface expression. Although glycosylation on CD44 had no effect, that on β1 integrin significantly affected association of β1 integrin with MT1-MMP. The results thus demonstrate that the cancer cells use multiple mechanisms for degradation of matrix in a controlled manner to couple it with movement for effective invasion.