• Login
    View Item 
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    Expression of MT1-MMP in Head and Neck Squamous Cell Carcinomas (HNSCCs) and Endothelial Cells is Regulated by Hypoxia and Semaphorin 4D (Sema4D)

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Bugshan_umaryland_0373D_10730.pdf
    Size:
    17.00Mb
    Format:
    PDF
    Download
    Author
    Bugshan, Amr
    0000-0001-7920-4556
    Advisor
    Basile, John R.
    Date
    2016
    Type
    dissertation
    
    Metadata
    Show full item record
    Abstract
    Membrane type 1 matrix metalloproteinase (MT1-MMP) is an integral membrane protein that is important in tumor growth, migration, and invasion. It has the ability to degrade ECM, non-matrix proteins such as CD44 and integrin, and activate MMP2. Semaphorin 4D (Sema4D), a membrane-bound semaphorin, is highly expressed in malignancies such as head and neck squamous cell carcinoma (HNSCC) and is known to be pro-angiogenic, promoting the growth of blood vessels into a developing tumor by acting as a chemoattractant when bound to its receptor, Plexin-B1 (PB1), on endothelial cells. Our central hypothesis is that tumor hypoxia causes an increase in Sema4D, which acts in an autocrine and paracrine manner on tumor cells to induce the overexpression of MT1-MMP, which, in turn, cleaves Sema4D and increases availability to the tumor microenvironment to promote tumor-induced angiogenesis and invasion. Using immunoblots and flow cytometry, we demonstrate that MT1-MMP increases in HNSCC cells in a Sema4D and Plexin-B1-dependent manner in hypoxia. Also, we show that RhoA and NF-?B (downstream effectors of Plexin-B1) are important in the regulation of cell surface MT1-MMP expression under hypoxic conditions. Consequently, tumor-induced invasion and angiogenesis are enhanced. Soluble Sema4D diffuses out from the tumor and acts as a chemoattractant for endothelial cells, which also upregulate MT1-MMP on their surface to facilitate migration through the extracellular matrix. We conclude that Sema4D controls its own availability and, therefore, its own pro-angiogenic potential through autocrine/paracrine regulation of MT1-MMP.
    Description
    University of Maryland, Baltimore. Oral and Experimental Pathology. Ph.D. 2016
    Keyword
    head and neck squamous cell carcinoma
    MMP14
    MT1-MMP
    Plexin-B1
    Semaphorin 4D
    Endothelial Cells
    Matrix Metalloproteinase 14
    Semaphorins
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/5453
    Collections
    Theses and Dissertations All Schools
    Theses and Dissertations School of Dentistry

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.