Podoplanin is involved in the prognosis of head and neck squamous cell carcinoma through interaction with VEGF-C.

We investigated the clinical significance of podoplanin expression in relation to clinicopathological variables in head and neck squamous cell carcinoma (HNSCC), to determine its effectiveness as a marker for high-risk HNSCC patients. Upregulation of podoplanin in HNSCC tissues was examined using immunohistochemistry and clinicopathological analyses. Wound healing and invasion assays were performed using HNSCC cells that were transfected with podoplanin siRNA, podoplanin vector and cotransfection with both the podoplanin vector and VEGF-C siRNA. High podoplanin expression was significantly associated with ~3- and 5-fold increases in the presence of positive lymph node metastasis and poor histological grade, respectively (P<0.05). High levels of podoplanin expression were significantly associated with decreased overall and disease-specific survival rates (P<0.05). Furthermore, upregulation of podoplanin induced cell wound repair activity and invasiveness in the FaDu and SNU-1041 cells, respectively, while downregulation of podoplanin expression through VEGF-C silencing using co-transfection of both the podoplanin vector and VEGF-C siRNA suppressed cell wound healing and invasion abilities in the HNSCC cells. Our findings suggest that high podoplanin expression is associated with aggressive tumor behavior, poor prognosis and metastatic regulation through interaction with VEGF-C, suggesting that podoplanin may be used as a potential prognostic biomarker for HNSCC.