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Agalioti, Theodora; Giannou, Anastasios D.; Krontira, Anthi C.; Kanellakis, Nikolaos I.; Kati, Danai; Vreka, Malamati; Pepe, Mario; Spella, Magda; Lilis, Ioannis; Zazara, Dimitra E.; Nikolouli, Eirini; Spiropoulou, Nikolitsa; Papadakis, Andreas; Papadia, Konstantina; Voulgaridis, Apostolos; Harokopos, Vaggelis; Stamou, Panagiota; Meiners, Silke; Eickelberg, Oliver; Snyder, Linda A.; Antimisiaris, Sophia G.; Kardamakis, Dimitrios; Psallidas, Ioannis; Marazioti, Antonia;

Mutant KRAS promotes malignant pleural effusion formation

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  • Medientyp: E-Artikel
  • Titel: Mutant KRAS promotes malignant pleural effusion formation
  • Beteiligte: Agalioti, Theodora; Giannou, Anastasios D.; Krontira, Anthi C.; Kanellakis, Nikolaos I.; Kati, Danai; Vreka, Malamati; Pepe, Mario; Spella, Magda; Lilis, Ioannis; Zazara, Dimitra E.; Nikolouli, Eirini; Spiropoulou, Nikolitsa; Papadakis, Andreas; Papadia, Konstantina; Voulgaridis, Apostolos; Harokopos, Vaggelis; Stamou, Panagiota; Meiners, Silke; Eickelberg, Oliver; Snyder, Linda A.; Antimisiaris, Sophia G.; Kardamakis, Dimitrios; Psallidas, Ioannis; Marazioti, Antonia;
  • Erschienen: Springer Science and Business Media LLC, 2017
  • Erschienen in: Nature Communications
  • Sprache: Englisch
  • DOI: 10.1038/ncomms15205
  • ISSN: 2041-1723
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Malignant pleural effusion (MPE) is the lethal consequence of various human cancers metastatic to the pleural cavity. However, the mechanisms responsible for the development of MPE are still obscure. Here we show that mutant <jats:italic>KRAS</jats:italic> is important for MPE induction in mice. Pleural disseminated, mutant <jats:italic>KRAS</jats:italic> bearing tumour cells upregulate and systemically release chemokine ligand 2 (CCL2) into the bloodstream to mobilize myeloid cells from the host bone marrow to the pleural space via the spleen. These cells promote MPE formation, as indicated by splenectomy and splenocyte restoration experiments. In addition, <jats:italic>KRAS</jats:italic> mutations are frequently detected in human MPE and cell lines isolated thereof, but are often lost during automated analyses, as indicated by manual versus automated examination of Sanger sequencing traces. Finally, the novel <jats:italic>KRAS</jats:italic> inhibitor deltarasin and a monoclonal antibody directed against CCL2 are equally effective against an experimental mouse model of MPE, a result that holds promise for future efficient therapies against the human condition.</jats:p>
  • Zugangsstatus: Freier Zugang