Expression of TWEAK/Fn14 in neuroblastoma: Implications in tumorigenesis

Pettersen,Ingvild; Baryawno,Ninib; Abel,Frida; Bakkelund,Wenche  Helen; Zykova,Svetlana  N.; Winberg,Jan-Olof; Moens,Ugo; Rasmuson,Agnes; Kogner,Per; Johnsen,John  Inge; Sveinbjörnsson,Baldur

doi:10.3892/ijo.2013.1800

Expression of TWEAK/Fn14 in neuroblastoma: Implications in tumorigenesis

Authors:
- Ingvild Pettersen
- Ninib Baryawno
- Frida Abel
- Wenche Helen Bakkelund
- Svetlana N. Zykova
- Jan-Olof Winberg
- Ugo Moens
- Agnes Rasmuson
- Per Kogner
- John Inge Johnsen
- Baldur Sveinbjörnsson
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Affiliations: Translational Cancer Research Group, Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway, Childhood Cancer Research Unit, Department of Women and Children's Health, Karolinska Institutet, Stockholm, Sweden, Department of Clinical Genetics, The Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden, Department of Cell Biology and Histology, University of Tromsø, Tromsø, Norway, Department of Medical Biochemistry, University of Tromsø, Tromsø, Norway, Research Group of Molecular Inflammation, Institute of Medical Biology, University of Tromsø, Tromsø, Norway
Published online on: January 29, 2013 https://doi.org/10.3892/ijo.2013.1800
Pages: 1239-1248

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Abstract

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor (TNF) family of cytokines, acts on responsive cells via binding to a cell surface receptor called Fn14. TWEAK binding to an Fn14 receptor or constitutive Fn14 overexpression has been shown to activate nuclear factor κB signaling which is important in tumorigenesis and cancer therapy resistance. In the present study, we demonstrate that TWEAK and Fn14 are expressed in neuroblastoma cell lines and primary tumors, and both are observed at increased levels in high-stage tumors. The treatment of neuroblastoma cell lines with recombinant TWEAK in vitro causes increased survival, and this effect is partially due to the activation of NF-κB signaling. Moreover, TWEAK induces the release of matrix metalloprotease-9 (MMP-9) in neuroblastoma cells, suggesting that TWEAK may play a role in the invasive phase of neuroblastoma tumorigenesis. TWEAK-induced cell survival was significantly reduced by silencing the TWEAK and Fn14 gene functions by siRNA. Thus, the expression of TWEAK and Fn14 in neuroblastoma suggests that TWEAK functions as an important regulator of primary neuroblastoma growth, invasion and survival and that the therapeutic intervention of the TWEAK/Fn14 pathway may be an important clinical strategy in neuroblastoma therapy.

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