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Updated: Dec 8, 2025

The Clinical Application of Tumor Treating Fields Therapy in Glioblastoma
Published on: April 16, 2019
Tumor-Treating Fields Inhibit the Metastatic Potential of Osteosarcoma Cells
Ju Yeon Oh1, Yeon-Joo Lee2, Eun Ho Kim3
1Laboratory of Biochemistry, School of Life Sciences and Biotechnology, Korea University, Seongbuk-gu, Seoul, South Korea.
Abstract:
The prognosis of metastatic osteosarcoma (OS) remains poor with a <20% survival rate, particularly in cases of distant (non-lung) metastases. Tumor-treating field (TTF) therapy is a novel electric field-based treatment that causes metaphase arrest and tumor cell death, with the advantage of reduced side effects compared to radiation and chemotherapy. TTF shows promise in glioblastoma and other solid tumors; however, few studies have examined its potential in the treatment of osteosarcoma. Therefore, we explored the mechanism of TTF-induced metastasis inhibition and cell death using in vitro models. TTF (1.5 V/cm, 150 kHz) was applied to U2OS and KHOS/NP OS cell lines. In addition, a 3-dimensional culture system was established using these OS cell lines. Cell migration and invasion (i.e., metastatic potential) were examined using a wound-healing scratch assay and transwell assay, respectively. Western blotting of metastasis- and angiogenesis-related proteins was performed. TTF suppressed the migration of and invasion by OS cells and inhibited the expression of epithelial markers, thereby preventing epithelial-mesenchymal transition (EMT), a hallmark of metastasis. Moreover, TTF prevented angiogenesis in human tumor endothelial cells and downregulated matrix metalloproteinase-2 (MMP2) and vascular endothelial growth factor (VEGF) expression. Therefore, TTF shows potential as an improved treatment for osteosarcoma, warranting further preclinical studies in animal models to support clinical trials.
Insights
Tumor-treating field (TTF) therapy shows promise in inhibiting osteosarcoma (OS) metastasis and cell death. This novel electric field treatment suppressed OS cell migration, invasion, and angiogenesis, suggesting potential for improved patient outcomes.
Area of Science:
- Oncology
- Biophysics
- Cancer Metastasis Research
Background:
- Metastatic osteosarcoma (OS) has a poor prognosis, with limited treatment options for distant metastases.
- Tumor-treating field (TTF) therapy, an electric field-based treatment, has shown efficacy in other cancers but its role in OS is understudied.
Purpose of the Study:
- To investigate the mechanisms by which TTF inhibits metastasis and induces cell death in osteosarcoma.
- To evaluate the potential of TTF as a novel therapeutic strategy for metastatic osteosarcoma.
Main Methods:
- Applied TTF (1.5 V/cm, 150 kHz) to U2OS and KHOS/NP OS cell lines in 2D and 3D culture models.
- Assessed cell migration and invasion using wound-healing scratch and transwell assays.
- Analyzed metastasis- and angiogenesis-related proteins via Western blotting.
Main Results:
- TTF significantly suppressed OS cell migration and invasion, indicating reduced metastatic potential.
- TTF inhibited epithelial-mesenchymal transition (EMT) by affecting epithelial markers.
- TTF demonstrated anti-angiogenic effects and downregulated matrix metalloproteinase-2 (MMP2) and vascular endothelial growth factor (VEGF).
Conclusions:
- TTF therapy effectively inhibits osteosarcoma cell metastasis and angiogenesis in vitro.
- TTF demonstrates potential as an improved treatment modality for osteosarcoma.
- Further preclinical studies are warranted to support future clinical trials of TTF for osteosarcoma.

