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A Study of Head and Neck Squamous Cell Carcinoma Adhesion Mediated by Glycosphingolipids

Wood, S. Matthew
http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1314210756

Abstract Details

2011, Master of Science (MS), Ohio University, Biomedical Engineering (Engineering and Technology).
Cancer metastasis is the leading cause of cancer related deaths. It is a multistep process caused by cancer cells breaking away from the primary site and traveling through the lymphatic system or bloodstream, adhering to the endothelium and migrating through the endothelium to a new site. The molecular mechanisms concerning how cancer cells metastasize are not fully understood, with many gaps in the available information. It has been theorized that cancer cells may mimic and exploit similar mechanisms used by leukocytes in response to cytokine stimulation. Using the leukocyte adhesion cascade as a model, it is hypothesized that E-selectin a cell adhesion molecule (CAM) on endothelium and its ligands on cancer cells play a major role in metastasis of head and neck squamous cell carcinoma (HNSCC). Much research has been devoted to the study of sialofucosylated proteins as ligands for E-selectin; this study elucidates the role of sialofucosylated glycosphingolipids as a ligand for E-selectin. All HNSCC cells bound to human umbilical vein endothelial cells (HUVECs) in an E-selectin dependent manner, as treatment of HUVECs with anti-E-selectin monoclonal antibody eliminated tethering. Treatment of HNSCC cells with the protease bromelain led to decreased rolling velocities on HUVECs compared to untreated HNSCC cells, without reducing tethering. HNSCC polar lipid extracts (PLE, i.e. glycosphingolipids) were found to possess sialofucosylated E-selectin ligands, as adhesion of E-selectin transfected cells to immobilized HNSCC cell PLE was eradicated after treatment with sialidase and fucosidase. Moreover, polystyrene microspheres coated with PLE (mimicking cellular presentation) tethered and rolled on HUVECs under flow, while negative control microspheres did not. These results taken together implicate that siaolofucosylated glycosphingolipids are the major E-selectin ligands expressed on HNSCC cells.
Monica Burdick, PhD (Advisor)
Fabian Benencia, PhD (Committee Member)
Kenneth Goodrum, PhD (Committee Member)
Ramiro Malgor, MD (Committee Member)
55 p.
Biomedical Engineering
HNSCC; glycosphingolipids; E-selectin;

Recommended Citations

Citations

  • Wood, S. M. (2011). A Study of Head and Neck Squamous Cell Carcinoma Adhesion Mediated by Glycosphingolipids [Master's thesis, Ohio University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1314210756

    APA Style (7th edition)

  • Wood, S.. A Study of Head and Neck Squamous Cell Carcinoma Adhesion Mediated by Glycosphingolipids. 2011. Ohio University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1314210756.

    MLA Style (8th edition)

  • Wood, S.. "A Study of Head and Neck Squamous Cell Carcinoma Adhesion Mediated by Glycosphingolipids." Master's thesis, Ohio University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1314210756

    Chicago Manual of Style (17th edition)

ohiou1314210756
498
© 2011, all rights reserved.
This open access ETD is published by Ohio University and OhioLINK.