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Determination of the Relative Potency of an Anti-TNF Monoclonal Antibody mAb by Neutralizing TNF Using an In Vitro Bioanalytical Method
Published on: September 16, 2017
The role of TNF-α in chordoma progression and inflammatory pathways
Sukru Gulluoglu1,2, Emre Can Tuysuz1,2, Mesut Sahin3
1Department of Medical Genetics, Yeditepe University Medical School, Koftuncu Sok. Acıbadem Mah. Istek Vakfi Kat: 3 34718 No: 57/1 Kadikoy, 34755, Istanbul, Turkey.
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.
Insights
Tumor necrosis factor-alpha (TNF-α) promotes chordoma progression by increasing cell migration, invasion, and chemo-resistance. Elevated TNF-α correlates with poor prognosis and tumor-promoting inflammation in chordoma patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Chordomas are aggressive primary bone tumors known for therapy resistance and high recurrence rates.
- These tumors can cause significant local destruction, posing a therapeutic challenge.
Purpose of the Study:
- To investigate the impact of tumor necrosis factor-alpha (TNF-α) on chordoma progression.
- To evaluate the relationship between TNF-α and clinical outcomes in chordoma patients.
Main Methods:
- Chordoma cells were treated with TNF-α, and effects on chemo-resistance, epithelial to mesenchymal transition (EMT), migration, and stem cell properties were assessed.
- Gene expression (qRT-PCR, microarray) and functional assays were employed.
- Correlation between TNF-α expression and patient clinicopathological features was analyzed.
Main Results:
- TNF-α enhanced chordoma cell migration, invasion, and chemo-resistance, alongside increased EMT marker expression and NF-κB activation.
- Enhanced tumor sphere and soft agar colony formation, indicative of stem-like properties, were observed.
- High TNF-α and TNFR1 expression correlated with tumor volume, poor survival, and elevated LIF, PD-L1, and Ki67 levels.
Conclusions:
- TNF-α may act as a prognostic biomarker for chordoma progression.
- Tumor-promoting inflammation, mediated by factors like TNF-α, appears crucial in chordoma advancement.
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