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A Study of the Impact of Membrane Organization of Glycosphingolipid E-selectin Ligands and Glycoproteins on Head and Neck Cancer Cell Adhesion to Vascular Endothelium

Marshall, Jocelyn R.
http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1313073422

Abstract Details

2011, Master of Science (MS), Ohio University, Biological Sciences (Arts and Sciences).
A previous study by the Burdick lab showed that head and neck squamous cell carcinoma (HNSCC) cells bind to vascular endothelium through an adhesive interaction between oncologic glycosphingolipids and endothelial E-selectin. It was also suggested that the GSL ligand activity may be inhibited due to steric hindrance by neighboring proteins as evidenced by a major increase in adhesion when HNSCC (JHU-013-SCC) cells were treated with a protease. This thesis project investigates that inhibitory interaction and analyzes the impact of lipid raft association of GSLs and nearby proteins on adhesion inhibition. Parallel plate flow chamber analysis showed that lipid raft disruption, as well as lentiviral silencing of CD44, induced statistically significant increases in tethering of JHU-013-SCC cells to E-selectin. It was shown that lipid raft disruption had a greater effect than CD44-silencing. CD44-silencing exhibited an effect on binding almost synonymous to protease treatment suggesting that CD44 is the sole protein contributor to the inhibition. In addition, it was shown that CD44 present on the surface of JHU-013-SCC cells is localized within the lipid raft microdomains, therefore increasing the efficacy of the inhibition due to its probable association with nearby E-selectin ligands. Overall, this study showed that CD44, found in lipid raft microdomains, is a major contributor to protein inhibition of GSL ligand-mediated adhesion of HNSCC cells to endothelial E-selectin.
Monica Burdick, PhD (Advisor)
Douglas Goetz, PhD (Committee Member)
Shiyong Wu, PhD (Committee Member)
Fabian Benencia, PhD (Committee Member)
Biochemistry; Biomedical Engineering; Biomedical Research; Cellular Biology; Chemical Engineering
glycolipid; lipid raft; head and neck cancer; metastasis; E-selectin; adhesion

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Citations

  • Marshall, J. R. (2011). A Study of the Impact of Membrane Organization of Glycosphingolipid E-selectin Ligands and Glycoproteins on Head and Neck Cancer Cell Adhesion to Vascular Endothelium [Master's thesis, Ohio University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1313073422

    APA Style (7th edition)

  • Marshall, Jocelyn. A Study of the Impact of Membrane Organization of Glycosphingolipid E-selectin Ligands and Glycoproteins on Head and Neck Cancer Cell Adhesion to Vascular Endothelium. 2011. Ohio University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1313073422.

    MLA Style (8th edition)

  • Marshall, Jocelyn. "A Study of the Impact of Membrane Organization of Glycosphingolipid E-selectin Ligands and Glycoproteins on Head and Neck Cancer Cell Adhesion to Vascular Endothelium." Master's thesis, Ohio University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1313073422

    Chicago Manual of Style (17th edition)

ohiou1313073422
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© 2011, all rights reserved.
This open access ETD is published by Ohio University and OhioLINK.