Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


kent1195663733.pdf (21.61 MB)

ETD Abstract Container

Abstract Header

CHARACTERIZATION OF UROKINASE PLASMINOGEN ACTIVATOR RECEPTOR (UPAR) AND INTEGRIN SUBUNITS IN BREAST CARCINOMA CELL LINES WITH DIVERSE INVASIVE CAPACITIES

Sloan Stakleff, Kimberly Denise
http://rave.ohiolink.edu/etdc/view?acc_num=kent1195663733

Abstract Details

2007, PHD, Kent State University, College of Biomedical Sciences.
Tumor cell invasion is a complex process that involves coordinated functions among several cellular processes including adhesion, migration and proteolysis. Key mediators of the invasion process are the urokinase plasminogen activator receptor (uPAR) and integrin a and b subunits. A model system of breast normal epithelial and invasive breast cancer cells with discriminate invasive capacities (minimal, moderate, and high) was used to evaluate the cells within a variety of indigenous extracellular matrices (ECMs). Morphologic features were characterized and compared for the cells under conditions of normal growth and to promote invasion (treatment with phorbol myristate acetate). Production levels of uPAR and integrin subunits (alpha2, alpha3, alpha5, alpha6, alphav, beta1, and beta3) were measured by Western blot analysis. Molecular associations between uPAR and integrin subunits were identified using co-immunoprecipitation. Comparisons of the cells under conditions of normal growth and promotion of invasion, morphologic differences were observed and correlated with the cellular invasive phenotypes. Significant increases in the numbers of rounded cells were indicative of the phenotype for the moderately and highly invasive cells. Transformation to a rounded morphology corresponded with a predominant decrease in the production of integrin a and b subunits. Assessment of the interactions between uPAR and integrin subunits revealed that the receptors were covalently associated. The covalent associations were determined to be through cysteinyl disulfide bonding since the thiol reducing agent beta-mercaptoethanol disrupted the interactions and generated integrin fragments. Increased levels of uPAR-integrin associations were prevalent for the invasive breast cancer cells in comparison to the normal breast epithelial cells. UPAR-integrin associations were influenced by the ECM substrates, most notably on vitronectin due to a vitronectin-binding site on uPAR. Decreased production of integrin subunits with concomitant increased uPAR-integrin association is supportive of a relationship between a reduction in adherence to the ECM microenvironment and the anchorage of uPAR at the cell surface to enhance proteolytic activity. Repeated identification of covalently associated uPAR-integrin complexes confirmed the fundamental role for integrins in securing uPAR to the cell membrane.
Kathleen Doane (Advisor)
225 p.
Biology, Cell
urokinase; integrin; receptor; morphology; cancer

Recommended Citations

Citations

  • Sloan Stakleff, K. D. (2007). CHARACTERIZATION OF UROKINASE PLASMINOGEN ACTIVATOR RECEPTOR (UPAR) AND INTEGRIN SUBUNITS IN BREAST CARCINOMA CELL LINES WITH DIVERSE INVASIVE CAPACITIES [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1195663733

    APA Style (7th edition)

  • Sloan Stakleff, Kimberly. CHARACTERIZATION OF UROKINASE PLASMINOGEN ACTIVATOR RECEPTOR (UPAR) AND INTEGRIN SUBUNITS IN BREAST CARCINOMA CELL LINES WITH DIVERSE INVASIVE CAPACITIES. 2007. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1195663733.

    MLA Style (8th edition)

  • Sloan Stakleff, Kimberly. "CHARACTERIZATION OF UROKINASE PLASMINOGEN ACTIVATOR RECEPTOR (UPAR) AND INTEGRIN SUBUNITS IN BREAST CARCINOMA CELL LINES WITH DIVERSE INVASIVE CAPACITIES." Doctoral dissertation, Kent State University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=kent1195663733

    Chicago Manual of Style (17th edition)

kent1195663733
383
© 2007, all rights reserved.
This open access ETD is published by Kent State University and OhioLINK.
Release 3.2.12