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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. | LitMetric

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.

Biomed Res Int

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

Published: May 2015

AI Article Synopsis

  • Matrix remodeling and invasion of the basement membrane are key factors in how cancer progresses, with matrix-degrading enzymes playing a crucial role in this process.
  • In a study involving B16F10 and its invasive variant B16BL6 cells, it was found that β1,6 branched N-oligosaccharides enhance cell adhesion and promote the secretion of the enzyme MMP9.
  • The research indicated that while uPAR levels were similar in both cell lines, B16BL6 cells had significantly higher MT1-MMP expression, and alterations in glycosylation of receptors like β1 integrin affected their ability to associate with MT1-MMP, impacting the cells' invasion potential.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144153PMC
http://dx.doi.org/10.1155/2014/804680DOI Listing

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