title: Podoplanin is involved in the prognosis of head and neck squamous cell carcinoma through interaction with VEGF-C.
abstract: 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.
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Cancer Research Institute, Research Institute for Medical Sciences, Chungnam National University College of Medicine, Daejeon 301-721, Republic of Korea.
authors.forename: Hyun-Yi
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Cancer Research Institute, Research Institute for Medical Sciences, Chungnam National University College of Medicine, Daejeon 301-721, Republic of Korea.
authors.forename: Ki-Sang
authors.initials: KS
authors.lastname: Rha
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Cancer Research Institute, Research Institute for Medical Sciences, Chungnam National University College of Medicine, Daejeon 301-721, Republic of Korea.
authors.forename: Geun Ae
authors.initials: GA
authors.lastname: Shim
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Cancer Research Institute, Research Institute for Medical Sciences, Chungnam National University College of Medicine, Daejeon 301-721, Republic of Korea.
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pathology, Chungnam National University College of Medicine, Daejeon 301-721, Republic of Korea.
authors.forename: Jin-Man
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Department of Pathology, Chungnam National University College of Medicine, Daejeon 301-721, Republic of Korea.
authors.forename: Song Mei
authors.initials: SM
authors.lastname: Huang
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Cancer Research Institute, Research Institute for Medical Sciences, Chungnam National University College of Medicine, Daejeon 301-721, Republic of Korea.
authors.forename: Bon Seok
authors.initials: BS
authors.lastname: Koo
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D011379:Prognosis; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis / Q000235:genetics*; D014945:Wound Healing; D000098853:Podoplanin
chemical_list: D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; D042582:Vascular Endothelial Growth Factor C; C117468:PDPN protein, human; D000098853:Podoplanin