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Growth differentiation factor 15 as a radiation‐induced marker in oral carcinoma increasing radiation resistance
Author(s) -
Schiegnitz Eik,
Kämmerer Peer W.,
Rode Katharina,
Schorn Thomas,
Brieger Jürgen,
AlNawas Bilal
Publication year - 2016
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12323
Subject(s) - radioresistance , cell culture , apoptosis , cell , gdf15 , cell growth , biology , carcinogenesis , staining , microbiology and biotechnology , gene knockdown , cancer research , pathology , growth differentiation factor , medicine , cancer , endocrinology , biochemistry , genetics , gene , bone morphogenetic protein
Background Growth differentiation factor 15 ( GDF 15) is involved in tumor pathogenesis of oral squamous cell carcinoma ( OSCC ). The aim of this study was an investigation of the potential influence of GDF 15 on radioresistance of OSCC cells in vitro . Methods Oral squamous cell carcinoma cell lines were irradiated with 0, 2, or 6 Gy, and GDF 15 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 GDF 15 expression using immunofluorescent staining. For further investigation of GDF 15 effects on radioresistance, a GDF 15 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 GDF 15 expression in 5 OSCC cell lines compared with human gingival epithelial cells. Irradiation with two and six gray resulted in a significant elevation of GDF 15 expression per survived cell colony in the irradiated OSCC cell lines ( P < 0.001). Furthermore, a dose‐dependent expression of GDF 15 was seen. Immunofluorescent staining confirmed an elevated GDF 15 expression in irradiated OSCC cell lines ( n = 10; P ≤ 0.001). Apoptotic activity was significantly increased after irradiation in the GDF 15 knockdown group compared with control cells ( n = 24; P < 0.001). Conclusion This study describes for the first time the vital role of GDF 15 both in tumorigenesis and in radioresistance of OSCC cells. With its anti‐apoptotic effects, GDF 15 possibly promotes tumor progression and might protect carcinoma cells against irradiation effects. Consequently, GDF 15 may be a promising therapeutic target in oral cancer.