Tweety-homolog 1 drives brain colonization of gliomas

• Verfasst von: Jung, Erik [VerfasserIn]
• Verfasst von: Osswald, Matthias [VerfasserIn]
• Verfasst von: Sahm, Felix [VerfasserIn]
• Verfasst von: Schmenger, Torsten [VerfasserIn]
• Verfasst von: Solecki, Gergely [VerfasserIn]
• Verfasst von: Deumelandt, Katrin [VerfasserIn]
• Verfasst von: Kurz, Felix T. [VerfasserIn]
• Verfasst von: Xie, Ruifan [VerfasserIn]
• Verfasst von: Heuer, Sophie [VerfasserIn]
• Verfasst von: Thomé, Carina [VerfasserIn]
• Verfasst von: Syed, Mustafa [VerfasserIn]
• Verfasst von: Huber, Peter E. [VerfasserIn]
• Verfasst von: Heiland, Sabine [VerfasserIn]
• Verfasst von: Platten, Michael [VerfasserIn]
• Verfasst von: Deimling, Andreas von [VerfasserIn]
• Verfasst von: Wick, Wolfgang [VerfasserIn]
• Verfasst von: Winkler, Frank [VerfasserIn]
• Titel: Tweety-homolog 1 drives brain colonization of gliomas
• Verf.angabe: Erik Jung, Matthias Osswald, Jonas Blaes, Benedikt Wiestler, Felix Sahm, Torsten Schmenger, Gergely Solecki, Katrin Deumelandt, Felix T. Kurz, Ruifan Xie, Sophie Weil, Oliver Heil, Carina Thomé, Miriam Gömmel, Mustafa Syed, Peter Häring, Peter E. Huber, Sabine Heiland, Michael Platten, Andreas von Deimling, Wolfgang Wick, and Frank Winkler
• E-Jahr: 2017
• Jahr: July 19, 2017
• Umfang: 14 S.
• Fussnoten: Gesehen am 15.08.2018
• Titel Quelle: Enthalten in: The journal of neuroscience
• Ort Quelle: Washington, DC : Soc., 1981
• Jahr Quelle: 2017
• Band/Heft Quelle: 37(2017), 29, Seite 6837-6850
• ISSN Quelle: 1529-2401
• DOI: doi:10.1523/JNEUROSCI.3532-16.2017
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: glioblastoma
• Sach-SW: glioma
• Sach-SW: invasion
• Sach-SW: migration
• Sach-SW: Ttyh1
• Sach-SW: tumor microtubes
• K10plus-PPN: 1580061656

Abstract

Early and progressive colonization of the healthy brain is one hallmark of diffuse gliomas, including glioblastomas. We recently discovered ultralong (>10 to hundreds of microns) membrane protrusions [tumor microtubes (TMs)] extended by glioma cells. TMs have been associated with the capacity of glioma cells to effectively invade the brain and proliferate. Moreover, TMs are also used by some tumor cells to interconnect to one large, resistant multicellular network. Here, we performed a correlative gene-expression microarray and in vivo imaging analysis, and identified novel molecular candidates for TM formation and function. Interestingly, these genes were previously linked to normal CNS development. One of the genes scoring highest in tests related to the outgrowth of TMs was tweety-homolog 1 (TTYH1), which was highly expressed in a fraction of TMs in mice and patients. Ttyh1 was confirmed to be a potent regulator of normal TM morphology and of TM-mediated tumor-cell invasion and proliferation. Glioma cells with one or two TMs were mainly responsible for effective brain colonization, and Ttyh1 downregulation particularly affected this cellular subtype, resulting in reduced tumor progression and prolonged survival of mice. The remaining Ttyh1-deficient tumor cells, however, had more interconnecting TMs, which were associated with increased radioresistance in those small tumors. These findings imply a cellular and molecular heterogeneity in gliomas regarding formation and function of distinct TM subtypes, with multiple parallels to neuronal development, and suggest that Ttyh1 might be a promising target to specifically reduce TM-associated brain colonization by glioma cells in patients.