Career Development Program
Project Five: Roles of Head and Neck Cancer Stem Cells in Metastasis
Silvana Papagerakis, M.D., Ph.D.
The mortality associated with head and neck squamous cell carcinoma (HNSCC) is still unacceptably high and it remains among the highest of the major solid cancers. Despite improvements in the local control of HNSCC, many patients continue to die from this disease duet ot the development of distant metastasis. Novel prognostic tools and therapeutic approaches are greatly needed.
The identification of cancer stem cells (CSC) as the highly tumorigenic cell subpopulation in human cancers has created a new area of research with promising applications in cancer prognosis and therapeutics. We were first to isolate CSC from HNSCC using the cell surface marker CD44 and flow cytometry. It si not known if CSCs are the metastatic population, nor is it known how they carry out the metastatic process. We have highly exciting preliminary data indicating that CD44 positive cells can bind to endothelial cells (EC) under conditions of flow and have higher invasive potential when compared with other HNSCC subpopulations. We postulate that CSC preferentially express ligands (sLeX) that bind to EC and have increased invasive ability which allows these cells to leave the circulation to form metastatic deposits. The role of sLeX in HNSCC endothelial adhesion, and more specifically HNSCC stem cell adhesion, has not been characterized. This molecule may provide a unique and novel target for the prevention of metastasis.
We believe the work proposed is novel, exciting and important that addresses significant unknowns about the roles that CSC may play in HNSCC metastasis formation and its relationship with other metastatic biomarkers such as sLeX. This study also determines if inhibition of sLeX expression plays a bona fide role in the conversion of CSC HNSCC to a less aggressive progression towards metastasis formation.
These efforts will provide foundation for the design of novel therapeutic approaches, resulting in improvement of HNSCC management and patient outcome and will evaluate if CD44 and sLeX expression could be reliable biomarkers for metastasis potential. Their potential predictive value for the clinical outcome and patient survival will be subsequently tested in our patient population. An increased understanding of the molecular basis for treatment will allow better control of metastases by their earlier detection and prognosis.