Abstract
Objective: Disseminated head and neck cancer is still considered incurable, as therapeutic options for advanced metastatic head and neck squamous cell carcinomas (HNSCC) are limited. It is not known if CSCs are the metastatic population, nor how they carry out the metastatic process. Our previous studies indicated that metastatic HNSCC express high levels of an endothelial adhesion molecule, Sialyl-Lewis-X (sLeX, the main E-selectin ligand) with a critical role in the initiation of the metastatic dissemination, and that CSCs are significantly more motile and migratory. This study addresses important unknowns about the sLeX relationship with CSC.
Method: A panel of stage- and anatomic site-specific primary and metastatic HNSCC cell lines was examined by flow cytometry to quantify cell-surface sLeX expression comparatively with known CSC markers. HNSCC-derived sLeX-positive cells were injected in the flank of immunodeficient mice to evaluate their tumorigenic potential. Preparations of the cultured cells, and tumor specimens were immunohistochemically stained for sLeX and CSC markers.
Results: HNSCC originating from oral cavity expressed high sLeX that increased with advanced stage and poorer clinical outcomes. A small subpopulation of the sLeX positive cells was also positive for CCS markers. Flank injections of sLeX-positive tumor cells developed SCC in immunodeficient mice. sLeX-positive murine primary and metastatic tumors were also positive for CSC markers.
Conclusion: These studies suggest that sLeX could serve as a biomarker for CSC metastatic potential and provide foundation for the design of novel therapeutic approaches, resulting in improvement of HNSCC management and patient outcome.
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