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 Aug 14;12(8):e0183136. doi: 10.1371/journal.pone.0183136. eCollection 2017.

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 immunofluorescence, western blotting, and flow cytometry. In a sub-group 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.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology*
  • Adenocarcinoma of Lung
  • Aged
  • Aged, 80 and over
  • Female
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Lamin Type A / metabolism*
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Mucin-1 / metabolism
  • Neoplasm Metastasis
  • Pleural Effusion / metabolism*
  • Pleural Effusion / pathology*
  • World Health Organization

Substances

  • Lamin Type A
  • Mucin-1
  • lamin C

Grants and funding

This work was supported by an ARARD (Association Régionale d’Aide Respiratoire à Domicile) grant, Parc d'activités de Napollon, 100 avenue des Templiers, 13676 Aubagne Cedex, France. Tel: +33 442 848 701, Fax: +33 442 846 999 http://www.arard.asso.fr/vous-etes-patient.html. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.