Date of Award

Summer 1999

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Program/Concentration

Biomedical Sciences

Committee Director

Kenneth D. Somers

Committee Member

Timothy Bos

Committee Member

William J. Wasilenko

Committee Member

Ann E. Campbell

Committee Member

Mark S. Elliot

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a common malignant disease with poor prognosis. The majority of patients die from local invasion or lymphatic metastasis. The mechanism(s) underlining the invasiveness of HNSCC are poorly understood. Utilizing a panel of HNSCC cell lines previously established in our laboratory, we tested the application and relevance of the three-step hypothesis of tumor invasion to HNSCC and investigated the mechanism(s) pertaining to the regulation of each step in the invasive process. Data presented in this thesis demonstrated that tumor cell invasion in HNSCC is a complex process involving three repeated sequential steps: adhesion, proteolytic degradation of the basement membrane and other extracellular matrixes (ECMs), and cell migration. These three steps are linked and interdependent. For example, cell adhesion to the ECM triggers a series of signal transduction pathways that involve calcium mobilization, focal adhesion kinase (FAK) activation, and downstream events leading to alteration of cell function manifested by migration and matrix metal loproteinase (MMP) production. Our working model extends the previous three-step hypothesis for tumor invasion by underscoring FAK as an integrator of multiple signaling pathways. Efforts to determine the role of FAK in the integration and propagation of signal transduction pathways should lead to a better understanding of the molecular mechanisms for generating the invasive phenotype of HNSCCs which may, in turn, lead to the discovery of new targets for therapy of invasive HNSCC.

Comments

A Dissertation Submitted to the Faculty of Old Dominion University and Eastern Virginia Medical School in Partial Fulfillment of the requirement for the Degree of Doctor of Philosophy in Biomedical Science.

DOI

10.25777/cxsf-4q55

ISBN

9780599965980

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