TSC2 epigenetic defect in primary LAM cells. Evidence of an anchorage‐independent survival. Issue 5 (7th March 2014)

• Record Type: Journal Article
• Authors: Lesma, Elena; Ancona, Silvia; Sirchia, Silvia M.; Orpianesi, Emanuela; Grande, Vera; Colapietro, Patrizia; Chiaramonte, Eloisa; Di Giulio, Anna Maria; Gorio, Alfredo
• Is Part Of: Journal of cellular and molecular medicine. Volume 18:Issue 5(2014)
• Page Start: 766
• Page End: 779
• Publication Date: 2014-03-07
• Subjects: Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.12237
• Languages: English
• ISSNs: 1582-1838

Abstract

<abstract abstract-type="main" id="jcmm12237-abs-0001"> <title>Abstract</title> <p>Tuberous sclerosis complex (TSC) is caused by mutations in <italic>TSC1</italic> or <italic>TSC2</italic> genes. Lymphangioleiomyomatosis (LAM) can be sporadic or associated with TSC and is characterized by widespread pulmonary proliferation of abnormal α‐smooth muscle (ASM)‐like cells. We investigated the features of ASM cells isolated from chylous thorax of a patient affected by LAM associated with TSC, named LAM/TSC cells, bearing a germline <italic>TSC2</italic> mutation and an epigenetic defect causing the absence of tuberin. Proliferation of LAM/TSC cells is epidermal growth factor (EGF)‐dependent and blockade of EGF receptor causes cell death as we previously showed in cells lacking tuberin. LAM/TSC cells spontaneously detach probably for the inactivation of the focal adhesion kinase (FAK)/Akt/mTOR pathway and display the ability to survive independently from adhesion. Non‐adherent LAM/TSC cells show an extremely low proliferation rate consistent with tumour stem‐cell characteristics. Moreover, LAM/TSC cells bear characteristics of stemness and secrete high amount of interleukin (IL)‐6 and IL‐8. Anti‐EGF receptor antibodies and rapamycin affect proliferation and viability of non‐adherent cells. In conclusion, the understanding of LAM/TSC cell features is important in the assessment of cell invasiveness in LAM and TSC and should provide a useful model to test therapeutic approaches aimed at controlling their migratory ability.</p> </abstract>