Higher cMET dependence of sacral compared to clival chordoma cells: contributing to a better understanding of cMET in chordoma

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 c...

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Autores principales:	Birgit Lohberger, Susanne Scheipl, Ellen Heitzer, Franz Quehenberger, Danielle de Jong, Karoly Szuhai, Bernadette Liegl-Atzwanger, Beate Rinner
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8035117bd921477bb589f41c11a9927e
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spelling	oai:doaj.org-article:8035117bd921477bb589f41c11a9927e2021-12-02T17:13:27ZHigher cMET dependence of sacral compared to clival chordoma cells: contributing to a better understanding of cMET in chordoma10.1038/s41598-021-92018-02045-2322https://doaj.org/article/8035117bd921477bb589f41c11a9927e2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92018-0https://doaj.org/toc/2045-2322Abstract 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.Birgit LohbergerSusanne ScheiplEllen HeitzerFranz QuehenbergerDanielle de JongKaroly SzuhaiBernadette Liegl-AtzwangerBeate RinnerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Birgit Lohberger Susanne Scheipl Ellen Heitzer Franz Quehenberger Danielle de Jong Karoly Szuhai Bernadette Liegl-Atzwanger Beate Rinner Higher cMET dependence of sacral compared to clival chordoma cells: contributing to a better understanding of cMET in chordoma
description	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.
format	article
author	Birgit Lohberger Susanne Scheipl Ellen Heitzer Franz Quehenberger Danielle de Jong Karoly Szuhai Bernadette Liegl-Atzwanger Beate Rinner
author_facet	Birgit Lohberger Susanne Scheipl Ellen Heitzer Franz Quehenberger Danielle de Jong Karoly Szuhai Bernadette Liegl-Atzwanger Beate Rinner
author_sort	Birgit Lohberger
title	Higher cMET dependence of sacral compared to clival chordoma cells: contributing to a better understanding of cMET in chordoma
title_short	Higher cMET dependence of sacral compared to clival chordoma cells: contributing to a better understanding of cMET in chordoma
title_full	Higher cMET dependence of sacral compared to clival chordoma cells: contributing to a better understanding of cMET in chordoma
title_fullStr	Higher cMET dependence of sacral compared to clival chordoma cells: contributing to a better understanding of cMET in chordoma
title_full_unstemmed	Higher cMET dependence of sacral compared to clival chordoma cells: contributing to a better understanding of cMET in chordoma
title_sort	higher cmet dependence of sacral compared to clival chordoma cells: contributing to a better understanding of cmet in chordoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8035117bd921477bb589f41c11a9927e
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Higher cMET dependence of sacral compared to clival chordoma cells: contributing to a better understanding of cMET in chordoma

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