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  • Author(s):
    Maria V. Barbolina; Mijung Kim; Yueying Liu; Jaclyn Shepard; Abdelhak Belmadani; Richard J. Miller; Lonnie D. Shea; M. Sharon Stack
    Abstract:

    The majority of women diagnosed with epithelial ovarian carcinoma (EOC) succumb due to complications of metastatic disease, suggesting that antimetastatic therapies may improve patient survival. EOC metastasis involves intraperitoneal shedding of cells from the primary tumor, followed by adhesion and localized penetration of the submesothelial matrix to anchor metastatic implants. Accumulation of malignant ascites is also common. Thus, a unique microenvironmental niche is established, which i…

    Date Published:
    2010-03-25
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    Public
  • Author(s):
    L J Bannon, B L Cabrera, M S Stack, K J Green
    Abstract:

    Via their integration of the intermediate filament cytoskeleton into the cell membrane, desmosomes facilitate the maintenance of cell shape and tissue integrity as well as intercellular communication. The transmembrane components of the desmosome, the desmogleins and desmocollins, are members of the cadherin family of cell-cell adhesion molecules. Each of these proteins exists as three distinct isoforms, which are the products of individual genes and expressed in a cell-type and differentiati…

    Date Published:
    2001-11
    Record Visibility:
    Public
  • Author(s):
    Supurna Ghosh, Jennifer Koblinski, and M. Sharon Stack
    Abstract:

    Oral squamous cell carcinoma (OSCC) has 50% 5-year survival rate, highlighting our limited understanding of the molecular events that contribute to disease progression. Microarray analyses of primary oral tumors have identified urinary type plasminogen activator (uPA) and its receptor (uPAR) as key genes associated with human OSCC progression. The uPAR functions both as a proteinase receptor and an integrin ligand, modifying proteolysis, migration, integrin signaling and cellular transcriptio…

    Date Published:
    2010-02-01
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    Public
  • Author(s):
    Matthew J Ravosa 1, Ravinder Kunwar, Stuart R Stock, M Sharon Stack
    Abstract:

    Excessive, repetitive and altered loading have been implicated in the initiation of a series of soft- and hard-tissue responses or ;functional adaptations’ of masticatory and locomotor elements. Such adaptive plasticity in tissue types appears designed to maintain a sufficient safety factor, and thus the integrity of given element or system, for a predominant loading environment(s). Employing a mammalian species for which considerable in vivo data on masticatory behaviors are available, g…

    Date Published:
    2007-02-15
    Record Visibility:
    Public
  • Author(s):
    Natalie M Moss, Maria V Barbolina, Yueying Liu, Limin Sun, Hidayatullah G Munshi, M Sharon Stack
    Abstract:

    An early event in the metastasis of epithelial ovarian carcinoma is shedding of cells from the primary tumor into the peritoneal cavity followed by diffuse i.p. seeding of secondary lesions. Anchorage-independent metastatic cells are present as both single cells and multicellular aggregates (MCA), the latter of which adhere to and disaggregate on human mesothelial cell monolayers, subsequently forming invasive foci. Although this unique metastatic mechanism presents a distinct set of therapeu…

    Date Published:
    2009-09-01
    Record Visibility:
    Public
  • Author(s):
    Jochen H Lorch, Jodi Klessner, J Ken Park, Spiro Getsios, Yvonne L Wu, M Sharon Stack, Kathleen J Green
    Abstract:

    The epidermal growth factor receptor (EGFR) has been proposed as a key modulator of cadherin-containing intercellular junctions, particularly in tumors that overexpress this tyrosine kinase. Here the EGFR tyrosine kinase inhibitor PKI166 and EGFR blocking antibody C225, both of which are used clinically to treat head and neck cancers, were used to determine the effects of EGFR inhibition on intercellular junction assembly and adhesion in oral squamous cell carcinoma cells. EGFR inhibition res…

    Date Published:
    2004-08-27
    Record Visibility:
    Public
  • Author(s):
    Maria V Barbolina, Brian P Adley, Edgardo V Ariztia, Yueying Liu, M Sharon Stack
    Abstract:

    Late stage ovarian cancer is characterized by disseminated intraperitoneal metastasis as secondary lesions anchor in the type I and III collagen-rich submesothelial matrix. Ovarian carcinoma cells preferentially adhere to interstitial collagen, and collagen-induced integrin clustering up-regulates the expression of the transmembrane collagenase membrane type 1 matrix metalloproteinase (MT1-MMP). Collagenolytic activity is important in intraperitoneal metastasis, potentiating invasion through …

    Date Published:
    2007-02-16
    Record Visibility:
    Public
  • Author(s):
    Karen D Cowden Dahl, Jaime Symowicz, Yan Ning, Elisa Gutierrez, David A Fishman, Brian P Adley, M Sharon Stack, Laurie G Hudson
    Abstract:

    Epidermal growth factor (EGF) receptor (EGFR) is frequently elevated in epithelial ovarian cancer, and E-cadherin expression is often reduced in advanced disease. In this study, we investigated a mechanism by which EGFR activation promotes disruption of adherens junctions through induction of matrix metalloproteinase 9 (MMP-9). We show that EGFR activation down-modulates E-cadherin, and broad spectrum MMP inhibition ameliorates EGF-stimulated junctional disruption and loss of E-cadherin prote…

    Date Published:
    2008-06-15
    Record Visibility:
    Public
  • Author(s):
    Subhendu Mukhopadgyay, Hidayatullah G Munshi, Suman Kambhampati, Antonella Sassano, Leonidas C Platanias, M Sharon Stack
    Abstract:

    Matrix metalloproteinases (MMPs) play an important role in the invasive behavior of a number of cancers including oral squamous cell cancer (OSCC), and increased expression of MMP-9 is correlated with invasive and metastatic OSCC. Because calcium is an important regulator of keratinocyte function, the effect of modulating extracellular calcium on MMP-9 expression in OSCC cell lines was evaluated. Increasing extracellular calcium induced a dose-dependent increase in MMP-9 expression in immorta…

    Date Published:
    2004-08-06
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    Public
  • Author(s):
    Chen Wang, John T Norton, Supurna Ghosh, Julie Kim, Kazuo Fushimi, Jane Y Wu, M Sharon Stack, Sui Huang
    Abstract:

    RNA processing is altered during malignant transformation, and expression of the polypyrimidine tract-binding protein (PTB) is often increased in cancer cells. Although some data support that PTB promotes cancer, the functional contribution of PTB to the malignant phenotype remains to be clarified. Here we report that although PTB levels are generally increased in cancer cell lines from multiple origins and in endometrial adenocarcinoma tumors, there appears to be no correlation between PTB l…

    Date Published:
    2008-07-18
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    Public
  • Author(s):
    Hidayatullah G Munshi, Supurna Ghosh, Subhendu Mukhopadhyay, Yi I Wu, Ratna Sen, Kathleen J Green, M Sharon Stack
    Abstract:

    The expression and activity of epithelial proteinases is under stringent control to prevent aberrant hydrolysis of structural proteins and disruption of tissue architecture. E-cadherin-dependent cell-cell adhesion is also important for maintenance of epithelial structural integrity, and loss of E-cadherin expression has been correlated with enhanced invasive potential in multiple tumor models. To address the hypothesis that there is a functional link between E-cadherin and proteinase expressi…

    Date Published:
    2002-10-11
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    Public
  • Author(s):
    S M Ellerbroek, J M Halbleib, M Benavidez, J K Warmka, E V Wattenberg, M S Stack, L G Hudson
    Abstract:

    Activation of the epidermal growth factor (EGF) receptor regulates many processes associated with metastasis, including modulation of cell:cell and cell:substrate interactions, production of matrix-degrading proteinases, and cellular migration. We have demonstrated previously that EGF stimulates migration and matrix metalloproteinase (MMP)-9-dependent invasion of ovarian cancer cells. In this study, we compare the roles of EGF-induced phosphatidylinositol 3-kinase (PI3K) and mitogen-activated…

    Date Published:
    2001-03-01
    Record Visibility:
    Public