gms | German Medical Science

Objective: Tumor Treating Fields (TTFields) therapy is indicated to treat glioblastoma multiforme. The treatment delivers low intensity, intermediate frequency alternating electric fields to the brain. In the past, the anti-mitotic effects of TTFields have been studied intensively to clarify the mechanism of action. Here, we investigated additional effects of TTFields on cells such as invasion properties.

Methods: We used the inovitro system to treat human and mouse melanoma, human glioma, human colon cancer and human breast cancer cell lines with TTFields. A modified Matrigel coated Boyden chamber was used to conduct invasion assays. The effects of TTFields on cell size, stress fibers and focal adhesions morphology were studied by immuno-fluorescent confocal microscopy.

Results: We found that compared to untreated cells, invasion was significantly reduced in all tested cell lines. In addition, 300 kHz was determined as the optimal frequency to inhibit invasion, whereas 200 kHz was the optimal anti-mitotic frequency that resulted in death of glioma cells. Electric fields intensities of 0.6 V/cm RMS (which is below the 1 V/cm RMS threshold previously reported for induction of cell death) were found to affect migration. When Bumetanide (inhibits cellular motility) was combined with TTFields, invasion of glioma cells was further inhibited. Upon TTFields treatment an increase in cell volume and in size of focal adhesions was found as well as an increase in the number and peripheral distribution of adhesion sites. Cells treated with TTFields showed a decrease in the appearance of stress fibers and a dense meshwork of actin filaments around the entire cell periphery.

Conclusion: These results indicate that TTFields impair the motility of cancer cells. Field intensity and frequency required for maximal inhibition of cell motility differ from those necessary for anti-mitotic effects. As exposure to TTFields alters cell morphology this may be involved in the reduction of cell motility.