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Αgalioti, T.* ; Giannou, A.D.* ; Krontira, A.C.* ; Kanellakis, N.I.* ; Kati, D.* ; Vreka, M. ; Pepe, M. ; Spella, M.* ; Lilis, I.* ; Zazara, D.E.* ; Nikolouli, E.* ; Spiropoulou, N.* ; Papadakis, A.* ; Papadia, K.* ; Voulgaridis, A.* ; Harokopos, V.* ; Stamou, P.* ; Meiners, S. ; Eickelberg, O. ; Snyder, L.A.* ; Antimisiaris, S.G.* ; Kardamakis, D.* ; Psallidas, I.* ; Μarazioti, A.* ; Stathopoulos, G.T.

Mutant KRAS promotes malignant pleural effusion formation.

Nat. Commun. 8:15205 (2017)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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 KRAS is important for MPE induction in mice. Pleural disseminated, mutant KRAS 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, KRAS 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 KRAS 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Lung Adenocarcinoma Patients; Egfr Mutation Status; Mast-cells; Metastasis; Activation; Cancer; Carcinogenesis; Inflammation; Angiogenesis; Monocytes
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 8, Heft: , Seiten: , Artikelnummer: 15205 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus