作者: Cholpon S Djuzenova , Simon Memmel , Vladimir L Sukhorukov , Marcus Höring , Katherine Westerling
DOI: 10.1371/JOURNAL.PONE.0087052
关键词:
摘要: Glioblastoma multiforme (GBM) is characterized by rapid growth, invasion and resistance to chemo−/radiotherapy. The complex cell surface morphology with abundant membrane folds, microvilli, filopodia other extensions believed contribute the highly invasive behavior therapy of GBM cells. present study addresses mechanisms leading excessive area in five lines differing mutational status for PTEN p53. In addition scanning electron microscopy (SEM), folding were quantified dielectric measurements capacitance using single-cell electrorotation (ROT) technique. osmotic stability volume regulation cells analyzed video microscopy. expression PTEN, p53, mTOR several marker proteins involved growth synthesis examined Western blotting. combined SEM, ROT data provided independent evidence a large variability among tested lines. Thus, DK-MG (wild type p53 wild PTEN) exhibited lowest degree folding, probed area-specific Cm = 1.9 µF/cm2. contrast, carrying mutations both (U373-MG SNB19) showed highest values 3.7–4.0 µF/cm2, which corroborate well their heavily villated revealed SEM. Since are well-known inhibitors mTOR, increased area/folding mutant may be related enhanced protein lipid due deregulation mTOR-dependent downstream signaling pathway. Given that folds implicated tumor motility metastasis, approach presented here provides simple tool screening biophysical properties studies on targeting chemo- or radiotherapeutically migration types.