PT  - JOURNAL ARTICLE
AU  - Anthi Krontira
AU  - Malamati Vreka
AU  - Marianthi Iliopoulou
AU  - Ioannis Lilis
AU  - Theodora Agalioti
AU  - Nicoleta Spiropoulou
AU  - Georgia Giotopoulou
AU  - Yuval Rinkevich
AU  - Magda Spella
AU  - Georgios Stathopoulos
AU  - Antonia Marazioti
TI  - A conditional mouse model of malignant pleural mesothelioma
AID  - 10.1183/13993003.congress-2016.OA497
DP  - 2016 Sep 01
TA  - European Respiratory Journal
PG  - OA497
VI  - 48
IP  - suppl 60
4099  - http://erj.ersjournals.com/content/48/suppl_60/OA497.short
4100  - http://erj.ersjournals.com/content/48/suppl_60/OA497.full
SO  - Eur Respir J2016 Sep 01; 48
AB  - Malignant pleural mesothelioma (MPM) is a highly aggressive tumor caused by asbestos. Faithful mouse models of the disease are missing. Our aim was to develop and characterize a conditional and transplantable mouse model of MPM. Conditional mutant KRAS-expressing (LSL.KRASG12D; K) and TRP53-deleted (Trp53f/f; P) mice were intercrossed in all possible combinations, followed by intrapleural adenovirus-Cre. Efficient and widespread pleural recombination was verified using dual fluorescent Cre-reporter mice. Multiple cell lines were derived from primary MPM from KP mice and transplanted to C57BL/6 mice. KP mice developed multifocal lethal (median, 95%CI survival 40, 38-72 days) MPM with malignant pleural effusions (MPE; mean±SD volume 349±269 μL) involving both the visceral and parietal pleura and the mediastinum. KP-MPM expresses classical markers of human MPM and gives rise to multiple MPM cell lines (KPM). KPM are transplantable to C57BL/6 mice, leading to death (median, 95%CI survival 26, 25-28 days) and MPE (mean±SD volume 387±180 μL). ΔKRAS could be the tumor initiating gene of malignant pleural mesothelioma development and could present an important therapeutic target.European Research Council Starting Independent Investigator (#260524) and Proof-of-Concept (#679345) Grants.