Open AccessTSC 2 epigenetic defect in primary LAM cells. Evidence of an anchorage‐independent survival
Author(s) -
Lesma Elena,
Ancona Silvia,
Sirchia Silvia M.,
Orpianesi Emanuela,
Grande Vera,
Colapietro Patrizia,
Chiaramonte Eloisa,
Di Giulio Anna Maria,
Gorio Alfredo
Publication year - 2014
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12237
Subject(s) - epigenetics , microbiology and biotechnology , chemistry , biology , biochemistry , gene
Tuberous sclerosis complex ( TSC ) is caused by mutations in TSC 1 or TSC 2 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 TSC 2 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/m TOR 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.