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Cellular Oncology
Published in: Cellular Oncology 5/2019

01-10-2019 | Original Paper

The role of TNF-α in chordoma progression and inflammatory pathways

Authors: Sukru Gulluoglu, Emre Can Tuysuz, Mesut Sahin, Cumhur Kaan Yaltirik, Aysegul Kuskucu, Ferda Ozkan, Altay Burak Dalan, Fikrettin Sahin, Ugur Ture, Omer Faruk Bayrak

Published in: Cellular Oncology | Issue 5/2019

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Abstract

Purpose

Chordomas are highly therapy-resistant primary bone tumors that exhibit high relapse rates and may induce local destruction. Here, we evaluated the effects of tumor necrosis factor-alpha (TNF-α) on chordoma progression and clinical outcome.

Methods

Chordoma cells were treated with TNF-α after which its short- and long-term effects were evaluated. Functional assays, qRT-PCR and microarray-based expression analyses were carried out to assess the effect of TNF-α on chemo-resistance, epithelial to mesenchymal transition (EMT), migration, invasion and cancer stem cell-like properties. Finally, relationships between TNF-α expression and clinicopathological features were assessed in a chordoma patient cohort.

Results

We found that TNF-α treatment increased the migration and invasion of chordoma cells. Also, NF-κB activation was observed along with increased EMT marker expression. In addition, enhanced tumor sphere formation and soft agar colony formation were observed, concomitantly with increased chemo-resistance and CD338 marker expression. The TNF-α and TNFR1 expression levels were found to be significantly correlated with LIF, PD-L1 and Ki67 expression levels, tumor volume and a short survival time in patients. In addition, a high neutrophil to lymphocyte ratio was found to be associated with recurrence and a decreased overall survival.

Conclusions

From our data we conclude that TNF-α may serve as a prognostic marker for chordoma progression and that tumor-promoting inflammation may be a major factor in chordoma tumor progression.
Appendix
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Metadata
Title
The role of TNF-α in chordoma progression and inflammatory pathways
Authors
Sukru Gulluoglu
Emre Can Tuysuz
Mesut Sahin
Cumhur Kaan Yaltirik
Aysegul Kuskucu
Ferda Ozkan
Altay Burak Dalan
Fikrettin Sahin
Ugur Ture
Omer Faruk Bayrak
Publication date
01-10-2019
Publisher
Springer Netherlands
Published in
Cellular Oncology / Issue 5/2019
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-019-00454-y

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