Career Development Program
Project One: Implications of Stem Cells in Head and Neck Squamous Cell Carcinoma
Mark E. Prince, MD, FRCS(C)
Despite advances in treatment options for patients with head and neck squamous cell carcinoma (HNSCC), survival rates have not improved in over thirty years. Progress in developing effective treatments and preventive strategies for HNSCC has been limited by our knowledge of how this cancer arises and which cells are involved in its development and progression. There is accumulating evidence that tumor stem cells are the cells responsible for the development and growth of a variety of malignant tumors. Stem cells and malignant cells share many basic phenotypic features. Both can migrate or metastasize, are able to differentiate and have the capacity for replication that makes them essentially immortal. Tumor stem cells may be highly resistant to treatment and therefore have significant effects on treatment response and patient survival.
Recent investigations with human breast cancer have shown that the cell surface markers ESA, CD44 and CD24 are able to identify tumor stem cells. Isolation of tumor stem cells from HNSCC has not been done. Stem cells characteristically contain mechanisms that make them resistant to antineoplastic treatment, including multi- drug resistance mediated by the P-glycoprotein (PGP) family of membrane transporters. PGP expression has been identified in hematopoietic stem cells and may represent a tumor stem cell marker that is shared by other cell lineages as well.
Tumor stem cells will be isolated from HNSCC specimens cultivated in vivo using a NOD/SCID mouse model already developed to investigate breast cancer. Tumor stem cell markers previously identified in breast cancer will be used to select for tumor stem cells in HNSCC. PGP expression will also be investigated as a potential marker for tumor stem cells in HNSCC. Single cell suspensions of clonogenic cells expressing the cell markers of interest will be selected by flow cytometry. Implantation of these cells into the animal model will be used to assess the tumorigenicity of each cell population and their ability to replicate the original tumor heterogenecity.
Identifying cell markers that can prospectively identify tumor stem cells in HNSCC will have significant implications. Unique cell markers or other molecules expressed by the tumor stem cells could be targeted as a means of eliminating this critical population of cancer cells. The ability to prospectively identify tumor stem cells will dramatically improve our ability to treat and cure this devastating tumor.