Department of Medical Genetics, Yeditepe University Medical School, Koftuncu Sok. Acıbadem Mah. Istek Vakfi Kat: 3 34718 No: 57/1 Kadikoy, 34755, Istanbul, Turkey.
Department of Biotechnology, Institute of Science, Yeditepe University, 34755, Istanbul, Turkey.
Cell Oncol (Dordr). 2019 Oct;42(5):663-677. doi: 10.1007/s13402-019-00454-y. Epub 2019 Jun 7.
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.
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.
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.
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.
脊索瘤是一种高度耐药的原发性骨肿瘤，具有较高的复发率，并可能导致局部破坏。在这里，我们评估了肿瘤坏死因子-α（TNF-α）对脊索瘤进展和临床结果的影响。
在 TNF-α处理脊索瘤细胞后，评估其短期和长期作用。进行功能测定、qRT-PCR 和基于微阵列的表达分析，以评估 TNF-α对化疗耐药性、上皮-间充质转化（EMT）、迁移、侵袭和癌症干细胞样特性的影响。最后，在脊索瘤患者队列中评估 TNF-α表达与临床病理特征之间的关系。
我们发现 TNF-α处理增加了脊索瘤细胞的迁移和侵袭。还观察到 NF-κB 激活以及 EMT 标志物表达增加。此外，观察到增强的肿瘤球体形成和软琼脂集落形成，同时伴有化疗耐药性和 CD338 标志物表达增加。TNF-α和 TNFR1 的表达水平与 LIF、PD-L1 和 Ki67 的表达水平、肿瘤体积和患者的短生存时间显著相关。此外，高中性粒细胞与淋巴细胞比值与复发和总生存时间缩短有关。
从我们的数据中可以得出结论，TNF-α可以作为脊索瘤进展的预后标志物，并且肿瘤促进炎症可能是脊索瘤肿瘤进展的一个主要因素。
