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.
Highlights
Malignant cell identification and characterization in pleural effusions are essential for the diagnosis and management of patients affected by primary or metastatic cancer
Patients diagnosed with a metastatic pleural effusion from lung adenocarcinoma in our institution were prospectively recruited. 32 patients were enrolled because their pleural effusion contained at least 20% adenocarcinoma cells
These flow cytometry experiments identified a sub-population of metastatic lung adenocarcinoma cells lacking lamin A expression, and we showed that this decrease in lamin A expression was correlated with the loss of epithelial membrane antigen (EMA)/MUC-1
Summary
Malignant cell identification and characterization in pleural effusions are essential for the diagnosis and management of patients affected by primary or metastatic cancer In this context, the identification of new biomarkers is required to improve the differential diagnosis between cancer subtypes, to choose the most appropriate therapy, and to make prognostic correlations. Nuclear matrix results from chemical preparation, using high salt saline solution, and is composed of the peripheral nuclear lamina, an internal network of proteins and residual nucleolus. Mostly composed of lamin filament networks, and other proteins, such as ribonucleoproteins, nuclear mitotic apparatus (NuMA). Mostly composed of lamin filament networks, and other proteins, such as ribonucleoproteins, nuclear mitotic apparatus (NuMA). . . [7,8]
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