Alterations in human breast cancer adhesion-motility in response to changes in cell surface glycoproteins displaying α-L-fucose moieties

  • Authors:
    • Kun Yuan
    • Dennis Kucik
    • Raj K. Singh
    • Catherine M. Listinsky
    • Jay J. Listinsky
    • Gene P. Siegal
  • View Affiliations

  • Published online on: April 1, 2008     https://doi.org/10.3892/ijo.32.4.797
  • Pages: 797-807
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Abstract

Glycosylation of proteins plays multiple roles in cell-cell and cell-matrix interactions. Fucose is a monosaccharide associated with glycosylation events and is known to be over-expressed in many malignant tumors. By using α-L-fucosidase (α-L-fase), a glycosidase that specifically removes α-L-fucose (α-L-f), we have examined the potential effects of defucosylation on tumor functions, focusing on tumor progression in the context of the interaction of tumor cells with the extracellular microenvironment. In this submission, we report that α-L-fase treatment decreases, in static assays, tumor cell adhesion to a wide variety of ECM components including fibronectin, laminin, collagen I, hyaluronic acid and the complex human biomatrix, HuBiogel®. By immunofluorescence, co-localization of β1 integrin and α-L-f was found to decrease accordingly. Sialyl Lewis X, an α-L-f-containing tetrasaccharide, which modulates the rolling of leukocytes and tumor cells on endothelium, was found to be diminished on human breast cancer cells after α-L-fase treatment. Using a dynamic flow chamber system, we were able to determine that defucosylation impaired the rolling of mammary cancer cells on human umbilical vein endothelial cells while significantly increasing their flow speed. Further, the rolling capability of these defucosylated tumor cells was also impaired on purified E and P-selectin matrices. Based on these data, we hypothesize that decreased fucosylation impairs the interaction between tumor cells and their external milieu, which in turn, affects key cell functions modulating tumor progression. Building on our previous studies which demonstrated α-L-fase decreased tumor cell invasion while significantly reducing MMP-9 activity, when added to the fact that decreased adhesion on HUVEC occurs in the presence of α-L-fase also leads us to propose that defucosylation may modulate metastasis, and thus provides a promising additional glycobiotic target for novel therapies.

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April 2008
Volume 32 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Yuan K, Kucik D, Singh RK, Listinsky CM, Listinsky JJ and Siegal GP: Alterations in human breast cancer adhesion-motility in response to changes in cell surface glycoproteins displaying α-L-fucose moieties. Int J Oncol 32: 797-807, 2008.
APA
Yuan, K., Kucik, D., Singh, R.K., Listinsky, C.M., Listinsky, J.J., & Siegal, G.P. (2008). Alterations in human breast cancer adhesion-motility in response to changes in cell surface glycoproteins displaying α-L-fucose moieties. International Journal of Oncology, 32, 797-807. https://doi.org/10.3892/ijo.32.4.797
MLA
Yuan, K., Kucik, D., Singh, R. K., Listinsky, C. M., Listinsky, J. J., Siegal, G. P."Alterations in human breast cancer adhesion-motility in response to changes in cell surface glycoproteins displaying α-L-fucose moieties". International Journal of Oncology 32.4 (2008): 797-807.
Chicago
Yuan, K., Kucik, D., Singh, R. K., Listinsky, C. M., Listinsky, J. J., Siegal, G. P."Alterations in human breast cancer adhesion-motility in response to changes in cell surface glycoproteins displaying α-L-fucose moieties". International Journal of Oncology 32, no. 4 (2008): 797-807. https://doi.org/10.3892/ijo.32.4.797