title: Leukemia Inhibitory Factor Promotes Aggressiveness of Chordoma.
abstract: 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.
authors.forename: Sukru
authors.initials: S
authors.lastname: Gulluoglu
authors.forename: Mesut
authors.initials: M
authors.lastname: Sahin
authors.forename: Emre Can
authors.initials: EC
authors.lastname: Tuysuz
authors.forename: Cumhur Kaan
authors.initials: CK
authors.lastname: Yaltirik
authors.forename: Aysegul
authors.initials: A
authors.lastname: Kuskucu
authors.forename: Ferda
authors.initials: F
authors.lastname: Ozkan
authors.forename: Fikrettin
authors.initials: F
authors.lastname: Sahin
authors.forename: Ugur
authors.initials: U
authors.lastname: Ture
authors.forename: Omer Faruk
authors.initials: OF
authors.lastname: Bayrak
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002817:Chordoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D003131:Combined Modality Therapy; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics; D005260:Female; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D053605:Leukemia Inhibitory Factor / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D016207:Cytokines; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C507840:LIFR protein, human; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C085839:TNFAIP2 protein, human; D019859:Proto-Oncogene Proteins c-met