Growth differentiation factor 15 as a radiation-induced marker in oral carcinoma increasing radiation resistance
Authors
Eik Schiegnitz, Peer W. Kämmerer, Katharina Rode, Thomas Schorn, Jürgen Brieger, Bilal Al-Nawas
Institution
University Medical Center of the Johannes Gutenberg-University, Mainz
Country
Germany
Year
2015
Journal
Journal of Oral Pathology and Medicine
Abstract
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).
CONCLUSION: 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.