Abstract
Objective: Among the clinical challenges of head and neck squamous cell carcinomas (HNSCC), the morbidity and mortality of advanced oral cancer (OC) remains paramount. The molecular mechanism controlling OC progression and metastasis are thus key to the improvement of clinical outcomes. Metastatic dissemination begins with adhesion of circulating tumor cells to the E-selectin-expressing endothelium with high levels of the main E-selectin ligand, sLeX, having been implicated in various carcinomas. Our study represents the first investigation of the sLeX involvement in HNSCC dissemination.
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. Secreted sLeX expression was measured by Western-blot in serum-free conditioned medium. Quantitative real time PCR (qRT-PCR) was used to identify the fucosyl-transferases involved in sLeX neosynthesis in HNSCC. HNSCC invasive and migratory abilities were evaluated by Matrigel assays according with their sLeX expression levels.
Results: HNSCC originating from oral cavity (OC) expressed high sLeX that increased with advanced stage; it was highest in cells from recurrent (HNSCC14B) and metastatic (UMSCC103) tumors with known poor clinical outcomes. The expression of secreted sLeX was also high in OC supernatants. sLeX-positive tumor cells exhibited higher invasive potential than sLex-negative HNSCC.
Conclusion: Among various sites HNSCC, both cell-bound and soluble sLeX was predominantly expressed in OC carcinomas and associated with recurrent and metastatic tumors. The mechanism of sLeX involvement in OC progression is under investigation. A better understanding of the HNSCC dissemination will positively impact the clinical management.
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