Leukemia Inhibitory Factor Promotes Aggressiveness of Chordoma
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 LIF 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 LIF 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 LIF can facilitate tumor-promoting inflammation. Results indicate that LIF plays a role in maintaining cancer stem cells in chordomas.
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Leukemia inhibitory factor (LIF);
Document Type: Research Article
Department of Medical Genetics, Yeditepe University Medical School, Istanbul, Turkey
Department of Nanoscience and Nanoengineering, Institute of Science Ataturk University, Erzurum, Turkey
Department of Biotechnology, Institute of Science, Yeditepe University, Istanbul, Turkey
Department of Neurosurgery, Yeditepe University Medical School, Yeditepe University, Istanbul, Turkey
Department of Medical Pathology, Yeditepe University Medical School, Yeditepe University, Istanbul, Turkey
August 7, 2017
This article was made available online on February 28, 2017 as a Fast Track article with title: "Leukemia Inhibitory Factor Promotes Aggressiveness of Chordoma".
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