Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Lohberger, B; Scheipl, S; Heitzer, E; Quehenberger, F; de, Jong, D; Szuhai, K; Liegl-Atzwanger, B; Rinner, B.
Higher cMET dependence of sacral compared to clival chordoma cells: contributing to a better understanding of cMET in chordoma.
Sci Rep. 2021; 11(1): 12466
Doi: 10.1038/s41598-021-92018-0
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Lohberger Birgit
- Scheipl Susanne
- Co-Autor*innen der Med Uni Graz
- Heitzer Ellen
- Liegl-Atzwanger Bernadette
- Quehenberger Franz
- Rinner Beate
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Chordomas are rare slow growing, malignant bone tumors of the axial skeleton with no approved medical treatment. As the majority of chordomas express cMET and its ligand, HGF, and crosstalks between EGFR and MET-signaling exist, we aimed to explore cMET activity in chordoma cell lines and clinical samples. We investigated nine chordoma patients and four chordoma cell lines for cMET expression. Two clival and two sacral chordoma cell lines were tested for chromosomal abnormalities of the MET gene locus; we studied the influence of HGF on the autocrine secretion and migration behavior, as well as protein expression and phosphorylation. Two MET/ALK inhibitors were investigated for their effects on cell viability, cell cycle, cyclin alterations, apoptosis, and downstream signaling pathways. Moderate and strong expression of membrane and cytoplasmic cMET in chordoma patients and cell lines used, as well as concentration-dependent increase in phospho cMET expression after HGF stimulation in all four chordoma cell lines was shown. U-CH2, MUG-Chor1, and UM-Chor1 are polysomic for MET. Chordoma cell lines secreted EGF, VEGF, IL-6, and MMP9 upon HGF-stimulation. Sacral cell lines showed a distinct HGF-induced migration. Both inhibitors dose-dependently inhibited cell growth, induce apoptosis and cell-cycle arrest, and suppress downstream pathways. Heterogeneous responses obtained in our in vitro setting indicate that cMET inhibitors alone or in combination with other drugs might particularly benefit patients with sacral chordomas.
- Find related publications in this database (using NLM MeSH Indexing)
- Anaplastic Lymphoma Kinase - antagonists & inhibitors, metabolism
- Anilides - pharmacology, therapeutic use
- Apoptosis - drug effects
- Cell Line, Tumor - administration & dosage
- Cell Proliferation - drug effects
- Cell Survival - drug effects, genetics
- Chordoma - drug therapy, genetics, pathology
- Cranial Fossa, Posterior - administration & dosage
- Crizotinib - pharmacology, therapeutic use
- DNA Copy Number Variations - administration & dosage
- Gene Expression Regulation, Neoplastic - administration & dosage
- Hepatocyte Growth Factor - genetics, metabolism
- Humans - administration & dosage
- Protein Kinase Inhibitors - pharmacology, therapeutic use
- Proto-Oncogene Proteins c-met - antagonists & inhibitors, genetics, metabolism
- Pyridines - pharmacology, therapeutic use
- Sacrum - pathology
- Signal Transduction - drug effects
- Skull Base Neoplasms - drug therapy, pathology