Identification and Characterization of Determinants of Head and Neck Tumor Cell Invasion

<p>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.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Year dc:date.available

1999

Author dc:creator

• Wu, Yangguan

Contributors dc:contributor

• Kenneth D. Somers
• Timothy Bos
• William J. Wasilenko
• Ann E. Campbell
• Mark S. Elliot

• Focal adhesion kinase
• Head tumors
• Matrix metalloproteinase
• Neck tumors
• Squamous cell carcinoma
• Tumor cell
• Cell Biology
• Oncology

Identifier

9780599965980

OAI identifier oai:identifier

oai:digitalcommons.odu.edu:biomedicalsciences_etds-1095