Leukemia Inhibitory Factor Promotes Aggressiveness of Chordoma


GÜLLÜOĞLU Ş., Sahin M., Tuysuz E. C., Yaltirik C. K., Kuskucu A., Ozkan F., ...Daha Fazla

ONCOLOGY RESEARCH, cilt.25, sa.7, ss.1177-1188, 2017 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 25 Sayı: 7
  • Basım Tarihi: 2017
  • Doi Numarası: 10.3727/096504017x14874349473815
  • Dergi Adı: ONCOLOGY RESEARCH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1177-1188
  • Anahtar Kelimeler: Chordoma, Leukemia inhibitory factor (LIF), Tumor inflammation, Prognosis, DIFFERENTIAL EXPRESSION, FACTOR-RECEPTOR, GROWTH-FACTOR, SPINAL-CORD, CELL-LINE, C-MET, LIF, ACTIVATION, SURVIVAL, REVEALS
  • Marmara Üniversitesi Adresli: Hayır

Özet

Chordomas are rare tumors of the spine and skull base that are locally destructive and resistant to chemotherapy and radiation therapy, with a poor prognosis and limited therapeutic options. Chordoma patients have a long life expectancy with high mortality from the disease. Cancer stem cells, which are known to exist in chordomas, have extensive proliferative and self-renewal potential and are responsible for maintaining tumor heterogeneity along with chemotherapy and radiotherapy resistance. Leukemia inhibitory factor (LIF) has multiple functions in stem cell biology, the immune response, and cancer, and is potentially a key molecule that allows cancer stem cells to self-renew. The purpose of this study was to determine whether LT increases the aggressive traits of chordoma cells and leads to a poor prognosis in patients. Chordoma cell lines were treated with LIF, and functional tests were done. Twenty skull base chordoma samples were checked for levels of LT and a correlation with clinicopathological features. The whole transcriptome microarray was used to observe changes in gene expression. We observed increased migration, invasion, tumorosphere formation, colony formation, epithelial mesenchymal transition, and chemoresistance accompanied by a dramatic elevation in inflammatory gene networks and pathways in chordomas. The expression of LIF was associated with tumor size and a poorer overall survival. Microarray and quantitative real-time polymerase chain reaction assessments suggest that LIP can facilitate tumor-promoting inflammation. Results indicate that LT plays a role in maintaining cancer stem cells in chordomas.