The role of TNF-α in chordoma progression and inflammatory pathways.
Cell Oncol (Dordr)
; 42(5): 663-677, 2019 Oct.
Article
em En
| MEDLINE
| ID: mdl-31175552
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ósseas
/
Cordoma
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Fator de Necrose Tumoral alfa
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Transição Epitelial-Mesenquimal
Tipo de estudo:
Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Cell Oncol (Dordr)
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Turquia