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]
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

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.

Domaines: Cancer; Pneumologie et système respiratoire; Génomique, Transcriptomique et Protéomique [q-bio.GN]

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, 2017, 12 (8), pp.e0183136. ⟨10.1371/journal.pone.0183136⟩. ⟨hal-01597882⟩