title: Growth differentiation factor 15 as a radiation-induced marker in oral carcinoma increasing radiation resistance.
abstract: BACKGROUND
  Growth differentiation factor 15 (GDF15) is involved in tumor pathogenesis of oral squamous cell carcinoma (OSCC). The aim of this study was an investigation of the potential influence of GDF15 on radioresistance of OSCC cells in vitro.
  
  
  METHODS
  Oral squamous cell carcinoma cell lines were irradiated with 0, 2, or 6 Gy, and GDF15 expression in the supernatant per survived cell colony was examined with ELISA. Non-irradiated and OSCC cell lines irradiated with 6 Gy were evaluated for GDF15 expression using immunofluorescent staining. For further investigation of GDF15 effects on radioresistance, a GDF15 knockdown model in a human OSCC cell line was established, and apoptotic activity after radiation was measured using the Caspase-Glo 3/7 system.
  
  
  RESULTS
  ELISA and immunofluorescent staining indicated an increased GDF15 expression in 5 OSCC cell lines compared with human gingival epithelial cells. Irradiation with two and six gray resulted in a significant elevation of GDF15 expression per survived cell colony in the irradiated OSCC cell lines (P < 0.001). Furthermore, a dose-dependent expression of GDF15 was seen. Immunofluorescent staining confirmed an elevated GDF15 expression in irradiated OSCC cell lines (n = 10; P ≤ 0.001). Apoptotic activity was significantly increased after irradiation in the GDF15 knockdown group compared with control cells (n = 24; P < 0.001).
  
  
  CONCLUSIONS
  This study describes for the first time the vital role of GDF15 both in tumorigenesis and in radioresistance of OSCC cells. With its anti-apoptotic effects, GDF15 possibly promotes tumor progression and might protect carcinoma cells against irradiation effects. Consequently, GDF15 may be a promising therapeutic target in oral cancer.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Plastic Surgery, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Eik
authors.initials: E
authors.lastname: Schiegnitz
authors.affiliation: Department of Oral and Maxillofacial Surgery, Plastic Surgery, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.|Department of Oral and Maxillofacial Surgery, Plastic Surgery, University Medical Centre, Rostock, Germany.
authors.forename: Peer W
authors.initials: PW
authors.lastname: Kämmerer
authors.affiliation: Department of Oral and Maxillofacial Surgery, Plastic Surgery, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Rode
authors.affiliation: Department of Oral and Maxillofacial Surgery, Plastic Surgery, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schorn
authors.affiliation: Department of Otorhinolaryngology, Molecular Tumor Biology Laboratory, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Brieger
authors.affiliation: Department of Oral and Maxillofacial Surgery, Plastic Surgery, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Bilal
authors.initials: B
authors.lastname: Al-Nawas
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D055785:Gene Knockdown Techniques; D055436:Growth Differentiation Factor 15 / Q000096:biosynthesis* / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D000077195:Squamous Cell Carcinoma of Head and Neck; D014162:Transfection
chemical_list: D014408:Biomarkers, Tumor; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D020169:Caspases
keywords: GDF15; biomarker; oral cancer; oral squamous cell carcinoma; radiation resistance