• 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, Regulation, and Inhibition of Matriptase in Human B-cell Neoplasm

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Chou_umaryland_0373D_10338.pdf
    Size:
    3.394Mb
    Format:
    PDF
    Download
    Author
    Chou, Feng-Pai
    Advisor
    Lin, Chen-Yong
    Date
    2012
    
    Metadata
    Show full item record
    Abstract
    Matriptase, a type II transmembrane serine protease, possesses potent oncogenic activity when an imbalance to its cognate inhibitor, hepatocyte activator inhibitor-1 (HAI-1), is established in a transgenic mouse model. The oncogenic activity of matriptase is in part attributed to its role in activation of other oncogenic molecules, such as urokinase plasminogen activator (uPA) and hepatocyte growth factor (HGF). These matriptase substrates play important roles in extracellular matrix-degrading, cellular motility, cell growth, and angiogenesis. All of these biological events are important for the development and progression of human cancers. While most of matriptase studies have been focused on epithelial and carcinoma cells in which HAI-1 plays a pivotal role in regulation and inhibition of matriptase, growing evidence showed that matriptase may be also important in blood malignancies. In this dissertation, I examined matriptase and HAI-1 expression in human blood tumor specimens and a variety of hematological cell lines. Significant imbalanced expression of matriptase to HAI-1 was determined in aggressive type B-cell malignancies in vitro and in vivo. In contrast, the protease was not detected in several indolent B-cell lymphomas and hyperactive B-cells residing in lymph nodes. The absence of HAI-1 expression in aggressive B-cell cancers has impact to the current dogma of matriptase-HAI-1 pairing in epithelial cells. Additionally, I discovered hypoxia initiated matriptase zymogen activation in blood tumors, producing inhibitor free, enzymatic matriptase to shed into extracellular milieu. Increased reactive oxygen species (ROSs) may be attributed to hypoxia-induced matriptase activation while the zymogen activation can be reduced by pre-treating cells with ROSs scavengers. To further define the roles of matriptase in the development and progression of B-cell tumors, stable matriptase knockdown populations were created in lymphoma and myeloma lines, respectively. The matriptase knockdown cells showed to negatively affect cell growth in vitro and colony formation in methylcellulose-based culture. Besides, in mice xenograft model, matriptase-deficient cells grew in significantly slow rate and formed less tumor volume than the control group. In summary, deregulated matriptase play important roles to affect the tumor microenvironment which is favoring the growth and progression of B-cell lymphoma and multiple myeloma.
    Description
    University of Maryland, Baltimore. Biochemistry. Ph.D. 2012
    Keyword
    matriptase
    Antithrombins
    Lymphoma, B-Cell
    Multiple Myeloma
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/2142
    Collections
    Theses and Dissertations All Schools
    Theses and Dissertations School of Medicine

    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.