Electric Fields at Breast Cancer and Cancer Cell Collective Galvanotaxis

Kan Zhu,Gabriela G Loots,Brian Reid,Nicholas R Hum,Min Zhao,Qin Sun

doi:10.1038/s41598-020-65566-0

Abstract

Cancer growth interferes with local ionic environments, membrane potentials, and transepithelial potentials, resulting in small electrical changes in the tumor microenvironment. Electrical fields (EFs) have significant effects on cancer cell migration (galvanotaxis/electrotaxis), however, their role as a regulator of cancer progression and metastasis is poorly understood. Here, we employed unique probe systems to characterize the electrical properties of cancer cells and their migratory ability under an EF. Subcutaneous tumors were established from a triple-negative murine breast cancer cell line (4T1), electric currents and potentials of tumors were measured using vibrating probe and glass microelectrodes, respectively. Steady outward and inward currents could be detected at different positions on the tumor surface and magnitudes of the electric currents on the tumor surface strongly correlated with tumor weights. Potential measurements also showed the non-homogeneous intratumor electric potentials. Cancer cell migration was then surveyed in the presence of EFs in vitro. Parental 4T1 cells and metastatic sublines in isolation showed random migration in EFs of physiological strength, whereas cells in monolayer migrated collectively to the anode. Our data contribute to an improved understanding of breast cancer metastasis, providing new evidence in support of an electrical mechanism that promotes this phenomenon.

Highlights

Metastasis accounts for ~90% of mortality in breast cancer patients[1,2]
Our results demonstrated that electric fields naturally exist at the cell line derived tumor allograft (CDA) tumor surface, and 4T1 cells respond to the Electrical fields (EFs) of physiological strength in monolayer but not in isolation
Plotting all tumors together showed a significant linear correlation of current magnitude with tumor weight (r2 = 0.83, P = 0.004; Supplemental Fig. 1). These results revealed that tumor generate an electric field at the tumor surface, and the current intensity appears to increase as the tumors increase in size

Summary

Introduction

The last few decades have seen significant progress in understanding genetic, molecular and signaling mechanisms underpinning cancer cell migration. Despite this knowledge and implementation of advanced detection technologies, the prevalence of metastatic breast cancer at initial diagnosis has remained stagnant since 1975 in the United States[3,4,5,6]. Metastatic breast cancer cells have been shown to respond to EFs with www.nature.com/scientificreports significantly higher speed and migration directionality than less metastatic cells[26,27]. Our results demonstrated that electric fields naturally exist at the CDA tumor surface, and 4T1 cells respond to the EFs of physiological strength in monolayer but not in isolation. Metastatic sublines showed significant galvanotactic movement in EFs with subtle differences

Methods

Results

Conclusion