Tumor treating fields inhibit glioblastoma cell migration, invasion and angiogenesis

Eun Ho Kim; Hyo Sook Song; Seung Hoon Yoo; Myonggeun Yoon

doi:10.18632/oncotarget.11372

Tumor treating fields inhibit glioblastoma cell migration, invasion and angiogenesis

Eun Ho Kim, Hyo Sook Song, Seung Hoon Yoo, Myonggeun Yoon

School of Biomedical Engineering

Research output: Contribution to journal › Article › peer-review

74 Citations (Scopus)

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 anchoragedependent (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, HIF1a 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.

Original language	English
Pages (from-to)	65125-65136
Number of pages	12
Journal	Oncotarget
Volume	7
Issue number	40
DOIs	https://doi.org/10.18632/oncotarget.11372
Publication status	Published - 2016

Keywords

Angiogenesis
Glioblastoma multiforme
Metastasis
NF-kB
Tumor treating fields

ASJC Scopus subject areas

Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.18632/oncotarget.11372

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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 anchoragedependent (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, HIF1a 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.",

keywords = "Angiogenesis, Glioblastoma multiforme, Metastasis, NF-kB, Tumor treating fields",

author = "Kim, {Eun Ho} and Song, {Hyo Sook} and Yoo, {Seung Hoon} and Myonggeun Yoon",

note = "Funding Information: This work was supported by a National Research Foundation of Korea (NRF) grant (No. NRF-2014R1A1A3053958, NRF-2014029534) funded by the Korean government (MSIP) and by the Nuclear Safety Research Program through the Korea Foundation Of Nuclear Safety (KOFONS), a granted financial resource of the Nuclear Safety and Security Commission (NSSC), Republic of Korea (No. 1305033).",

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T1 - Tumor treating fields inhibit glioblastoma cell migration, invasion and angiogenesis

AU - Kim, Eun Ho

AU - Song, Hyo Sook

AU - Yoo, Seung Hoon

AU - Yoon, Myonggeun

N1 - Funding Information: This work was supported by a National Research Foundation of Korea (NRF) grant (No. NRF-2014R1A1A3053958, NRF-2014029534) funded by the Korean government (MSIP) and by the Nuclear Safety Research Program through the Korea Foundation Of Nuclear Safety (KOFONS), a granted financial resource of the Nuclear Safety and Security Commission (NSSC), Republic of Korea (No. 1305033).

PY - 2016

Y1 - 2016

N2 - 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 anchoragedependent (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, HIF1a 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.

AB - 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 anchoragedependent (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, HIF1a 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.

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Tumor treating fields inhibit glioblastoma cell migration, invasion and angiogenesis

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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