MOTILITY AND INVASIVE PROPERTIES OF LAM/TSC CELLS FROM CHYLOUS OF A LAM/TSC PATIENT

Mutations in TSC2 are common factors in the development of TSC. LAM can occur as a sporadic disorder or associated with TSC. We have isolated human TSC2-smooth-muscle-cells from chylous of a LAM/TSC patient (LAM/TSC cells). In these cells tuberin expression is related to a TSC2 epigenetic regulation, and proliferation and survival are EGF-dependent. Cancer metastasis results in altered cell motility and invasiveness and is modulated by Notch activity. Given the fact that LAM/TSC cells express mesenchymal features, and survive in adherent or nonadherent status, we studied their invasive properties and motility. LAM/TSC cells showed anoikis resistence in soft agar assay confirming their loss of contact inhibition and acquisition of anchorage independent survival. Cell motility appear to be related to tuberin expression since it was reduced by 5-azacytidine treatment. Rapamycin and anti-EGFR decreased the migration rate but at a slightly lower extent than 5-azacytidine. Adherent and nonadherent LAM/TSC cells invaded epithelial cell layers by feeder cell invasion assay with an increased of IL-6 and IL-8 secretion. LAM/TSC cells express Notch and its targets (e.i. Hes, Jagged 1,2) that are not regulated by specific inhibitors. In conclusion, LAM/TSC cells express invasive and migratory features which appear to be related to tuberin expression