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Low lamin A expression in lung adenocarcinoma cells from pleural effusions is a pejorative factor associated with high number of metastatic sites and poor performance status

Elise Kaspi 1, 2 Diane Frankel 1, 2 Julien Guinde 1, 3 Sophie Perrin 1 Sophie Laroumagne 3 Andrée Robaglia-Schlupp 2, 1, 4 Kevin Ostacolo 1 Karim Harhouri 1 Rachid Tazi-Mezalek 3 Joëlle Micallef 5, 6 Hervé Dutau 3 Pascale Tomasini 7, 8 Annachiara de Sandre-Giovannoli 1, 4 Nicolas Lévy 1, 4 Pierre Cau 1 Philippe Astoul 9, 3 Patrice Roll 1, 2
1 GMGF - Génétique Médicale et Génomique Fonctionnelle
2 Laboratoire de Biologie Cellulaire [Hôpital de la Timone - APHM]
APHM - Assistance Publique - Hôpitaux de Marseille, TIMONE - Hôpital de la Timone [CHU - APHM]
3 Hôpital Nord [CHU - APHM]
4 Département de génétique médicale [Hôpital de la Timone - APHM]
5 INT - Institut de Neurosciences de la Timone
6 CIC - Centre d'Investigation Clinique [Hôpital de la Conception - APHM]
7 Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM]
8 AMU - Aix Marseille Université
9 Division d'oncologie thoracique, Département des maladies pulmonaires
Abstract : The type V intermediate filament lamins are the principal components of the nuclear matrix, including the nuclear lamina. Lamins are divided into A-type and B-type, which are encoded by three genes, LMNA, LMNB1, and LMNB2. The alternative splicing of LMNA produces two major A-type lamins, lamin A and lamin C. Previous studies have suggested that lamins are involved in cancer development and progression. A-type lamins have been proposed as biomarkers for cancer diagnosis, prognosis, and/or follow-up. The aim of the present study was to investigate lamins in cancer cells from metastatic pleural effusions using immunoflu-orescence, western blotting, and flow cytometry. In a subgroup of lung adenocarcinomas, we found reduced expression of lamin A but not of lamin C. The reduction in lamin A expression was correlated with the loss of epithelial membrane antigen (EMA)/MUC-1, an epithelial marker that is involved in the epithelial to mesenchymal transition (EMT). Finally, the lamin A expression was inversely correlated with the number of metastatic sites and the WHO Performance status, and association of pleural, bone and lung metastatic localizations was more frequent when lamin A expression was reduced. In conclusion, low lamin A but not lamin C expression in pleural metastatic cells could represent a major actor in the development of metastasis, associated with EMT and could account for a pejorative factor correlated with a poor Performance status.
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Submitted on : Wednesday, December 20, 2017 - 5:14:21 PM
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Elise Kaspi, Diane Frankel, Julien Guinde, Sophie Perrin, Sophie Laroumagne, et al.. Low lamin A expression in lung adenocarcinoma cells from pleural effusions is a pejorative factor associated with high number of metastatic sites and poor performance status. PLoS ONE, Public Library of Science, 2017, 12 (8), pp.e0183136. ⟨10.1371/journal.pone.0183136⟩. ⟨hal-01597882⟩

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