title: Tumor treating fields inhibit glioblastoma cell migration, invasion and angiogenesis.
abstract: Treatment with alternating electric fields at an intermediate frequency (100-300 kHz), referred to as tumor treating fields (TTF) therapy, inhibits cancer cell proliferation. In the present study, we demonstrated that TTF application suppressed the metastatic potential of U87 and U373 glioblastoma cell lines via the NF-kB, MAPK and PI3K/AKT signaling pathways. Wound-healing and transwell assays showed that TTF suppressed cell migration and invasion compared with controls. Soft agar and three-dimensional culture assays showed that TTF inhibited both anchorage-dependent (cell proliferation) and anchorage-independent (colony formation) GBM cell growth. TTF dysregulated epithelial-to-mesenchymal transition-related genes, such as vimentin and E-cadherin, which partially accounted for TTF inhibition of cell migration and invasion. We further demonstrated that TTF application suppressed angiogenesis by downregulating VEGF, HIF1α and matrix metalloproteinases 2 and 9. TTF also inhibited NF-kB transcriptional activity. Collectively, our findings show that TTF represents a promising novel anti-invasion and anti-angiogenesis therapeutic strategy for use in GBM patients.
authors.affiliation: Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Eun Ho
authors.initials: EH
authors.lastname: Kim
authors.affiliation: Department of Bio-Convergence Engineering, Korea University, Seoul, Korea.
authors.forename: Hyo Sook
authors.initials: HS
authors.lastname: Song
authors.affiliation: Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Yoo
authors.affiliation: Department of Bio-Convergence Engineering, Korea University, Seoul, Korea.
authors.forename: Myonggeun
authors.initials: M
authors.lastname: Yoon
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000528:radiation effects*; D004599:Electric Stimulation Therapy; D060733:Electromagnetic Radiation; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology; D009389:Neovascularization, Pathologic
keywords: NF-kB; angiogenesis; glioblastoma multiforme; metastasis; tumor treating fields