ECE2016 Guided Posters Endocrine Tumours (10 abstracts)
Implication of Filamin A in pulmonary neuroendocrine tumors aggressiveness and progression
Eleonora Vitali 1 , Stefano Ferrero 2 , Erika Peverelli 3 , Giulia Veronesi 4 , Marco Alloisio 4 , Luigi Santambrogio 5 , Anna Spada 2 , Giovanna Mantovani 2 & Andrea Lania 2,
1Laboratory of Cellular and Molecular Endocrinology, IRCCS Clinical and Research Institute Humanitas, Rozzano, Italy; 2Pathology Unit, Fondazione IRCCS Ca’ Granda – Ospedale Maggiore Policlinico, Milano, Italy; 3Endocrinology Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ospedale Maggiore Policlinico, University of Milan, Milano, Italy; 4Thoracic and General Surgery Unit, Istituto Clinico Humanitas IRCCS, Rozzano, Italy; 5Thoracic Surgery Unit, Fondazione IRCCS Ca’ Granda – Ospedale Maggiore Policlinico, Milano, Italy; 6Endocrinology Unit, Department of Biomedical Sciences, Humanitas University and Humanitas Research Hospital, Rozzano, Italy.
Pulmonary neuroendocrine tumors (PNTs) comprise a spectrum of neoplasms, ranging from low grade carcinoids to the highly malignant small cell lung cancers. Several studies identified cytoskeleton protein Filamin A (FLNA) as determinant in cancer progression and metastasis. To date, the role of FLNA in PNTs aggressiveness and progression is still unknown.
To address this question, we decided: i) to evaluate FLNA expression in PNTs ranging from typical carcinoids to small cell lung carcinomas; ii) to manipulate FLNA expression in order to assess its possible influence on cell proliferation, cell adhesion and migration in PNTs cell lines (H727 cells) and primary cultures; iii) to focus on the possible interaction between FLNA and Rap1, a small GTPase implicated in the regulation of cell polarity and migration.
FLNA is highly expressed in PNTs with high malignant grade, this expression being the highest in small cell lung carcinomas. Interestingly, FLNA silencing reduces cyclin D1 levels in PNTs cells and H727 cells (−53±3 P<0.01 and −48±13, P<0.05 vs C-siRNA, respectively) and cell proliferation in H727 cells (−56%±10, P<0.01). In addition, FLNA-silenced H727 cells were characterized by a reduction in cell migration (−25±9%, P<0.05 vs C-siRNA) and by an increase in cell adhesion (+86±19 P<0.05 vs C-siRNA), thus confirming that FLNA is involved in the control of cell motility. Interestingly, FLNA and Rap1 co-localized in cellular protrusions and FLNA knocking down induces a significant increase in Rap1 expression (+72±17%, P<0,01 vs C-siRNA).
In conclusion, these results demonstrated that FLNA is involved in mediating PNT progression thus providing a possible diagnostic and therapeutic target.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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