Beschreibung:
Abstract The ability of glioblastoma cells to invade adjacent brain tissue remains one of the major obstacles in obtaining therapeutic success. The development of novel treatment modalities that hinder glioma cancer cell motility could therefore facilitate disease control. TTFields are an effective treatment modality delivered via continuous, noninvasive application of low intensity, intermediate frequency, alternating electric fields. This therapy is approved for the treatment of patients with glioblastoma. Previous investigations have shown that TTFields disrupt microtubules and septin filaments, both of which govern key roles in mitosis. The goal of this study was to evaluate the possible effect of TTFields on human glioma cell migration and invasion properties. Four human glioma cell lines: U-87 MG, A-172, LN-229, and LN-18 (ATCC, USA) were treated with TTFields (1.75 V/cm RMS, 200 kHz) for 24 hours using the inovitro system. Cell migration was measured using in vitro wound healing assays. These were analyzed with Image Pro Premier (Media Cybernetics, USA) to determine migration rates. Invasion assays were performed using modified Matrigel coated Boyden chamber. Cells were stained, photographed and counted using image J (NIH, USA). Application of TTFields in-vitro led to a significant reduction in both migratory and invasive phenotype in all tested cell lines. Specifically, cell migration velocity, as assessed by the wound healing assay, was significantly reduced in U-87 MG (60%, P<0.001), and in A-172 (33%, P<0.001) compared with untreated control cells. The number of invading cells, as assessed by the modified Boyden chamber assay, was reduced in U-87 MG (54%, P<0.01), A-172 (51%, P<0.001), LN-229 (52%, P<0.001) and in LN-18 (30%, P<0.001) compared with untreated control cells. Our results suggest that human glioma cell motility is impaired by exposure to TTFields. Further studies are needed to elucidate the mechanism by which TTFields disrupts cellular motility in glioma cancer cells. Citation Format: Rosa S. Schneiderman, Anna Shteingauz, Moshe Giladi, Tali Voloshin, Yaara Porat, Mijal Munster, Roni Blat, Eilon D. Kirson, Uri Weinberg, Yoram Palti. Tumor treating fields (TTFields) reduce migration and invasion properties of human glioma cancer cells in vitro. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5078.