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Giannou, A.D.* ; Marazioti, A.* ; Spella, M.* ; Kanellakis, N.I.* ; Apostolopoulou, H.* ; Psallidas, L.* ; Prijovich, Z.M.* ; Vreka, M.* ; Zazara, D.E.* ; Lilis, L.* ; Papaleonidopoulos, V.* ; Kairi, C.A.* ; Patmanidi, A.L.* ; Giopanou, J.* ; Spiropoulou, N.* ; Harokopos, V.* ; Aidinis, V.* ; Spyratos, D.* ; Teliousi, S.* ; Papadaki, H.* ; Taraviras, S.* ; Snyder, L.A.* ; Eickelberg, O. ; Kardamakis, D.* ; Iwakura, V.* ; Feyerabend, T.B.* ; Rodewald, H.R.* ; Kalomenidis, L.* ; Blackwell, T.S.* ; Agalloti, T.* ; Stathopoulos, G.T.

Mast cells mediate malignant pleural effusion formation.

J. Clin. Invest. 125, 2317-2334 (2015)
DOI
Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
Mast cells (MCs) have been identified in various tumors; however, the role of these cells in tumorigenesis remains controversial. Here, we quantified MCs in human and murine malignant pleural effusions (MPEs) and evaluated the fate and function of these cells in MPE development. Evaluation of murine MPE-competent lung and colon adenocarcinomas revealed that these tumors actively attract and subsequently degranulate MCs in the pleural space by elaborating CCL2 and osteopontin. MCs were required for effusion development, as MPEs did not form in mice lacking MCs, and pleural infusion of MCs with MPE-incompetent cells promoted MPE formation. Once homed to the pleural space, MCs released tryptase AB1 and IL-1 beta, which in turn induced pleural vasculature leakiness and triggered NF-kappa B activation in pleural tumor cells, thereby fostering pleural fluid accumulation and tumor growth. Evaluation of human effusions revealed that MCs are elevated in MPEs compared with benign effusions. Moreover, MC abundance correlated with MPE formation in a human cancer cell-induced effusion model. Treatment of mice with the c-KIT inhibitor imatinib mesylate limited effusion precipitation by mouse and human adenbcarcinoma cells. Together, the results of this study indicate that MCs are required for MPE formation and suggest that MC-dependent effusion formation is therapeutically addressable.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Factor-kappa-b; C-kit Gene; Lung Adenocarcinoma; Tumor Progression; Bone-marrow; Mouse Model; Stem-cells; Cancer; Mice; Inflammation
ISSN (print) / ISBN 0021-9738
e-ISSN 1558-8238
Journal Journal of Clinical Investigation
Quellenangaben Volume: 125, Issue: 6, Pages: 2317-2334 Article Number: , Supplement: ,
Publisher American Society of Clinical Investigation
Publishing Place Ann Arbor
Reviewing status Peer reviewed
Institute(s) Institute of Lung Health and Immunity (LHI)
German Center for Lung Research (DZL)