TSC2 epigenetic defect in primary LAM cells. Evidence of an anchorage-independent survival.
Bottom Line: 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.
Affiliation: Laboratory of Pharmacology, Dept. of Health Sciences, Università degli Studi di Milano, Milano, Italy.Show MeSH
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Mentions: Tumour cells migrate from mouse primary tumours through a process of EMT, and this process is dependent on an inflammatory microenvironment . Likewise, IL-6 promotes EMT in breast cancer cells, and SNAIL can induce IL-6 expression in keratinocytes [35,36]. Interleukin-8 and IL-6 production is regulated by PI3K and mitogen-activated protein kinase pathways, which are also involved in TSC cell deregulated functions [37–39]. Interleukin-1α, IL-6 and IL-8 were secreted by LAM/TSC cells as the inhibition of protein biosynthesis by incubation with cycloheximide prevented their secretion (Fig. 7A–C). The release of the interleukins was, however, not significantly affected by rapamycin or anti-EGFR antibody exposure. Interleukin-6, IL-8 and IL-1α secretion was inhibited by the incubation with 5-azacytidine leading to tuberin expression (Fig. 7D–F). As expected, methylprednisolone and repertaxin, an antagonist of IL-8 receptor, effectively reduced the release of interleukins  (Fig. 7A–C). Interleukin-1β was not detectable.
Affiliation: Laboratory of Pharmacology, Dept. of Health Sciences, Università degli Studi di Milano, Milano, Italy.