Galvanotactic Migration of Glioblastoma and Brain Metastases Cells

Abstract

Galvanotaxis, the migration along direct current electrical fields, may contribute to the invasion of brain cancer cells in the tumor-surrounding tissue. We hypothesized that pharmacological perturbation of the epidermal growth factor (EGF) receptor and downstream phosphatidylinositol 3-kinase (PI3K)/AKT pathway prevent galvanotactic migration. In our study, patient-derived glioblastoma and brain metastases cells were exposed to direct current electrical field conditions. Velocity and direction of migration were estimated. To determine the effects of EGF receptor antagonist afatinib and AKT inhibitor capivasertib, assays of cell proliferation, apoptosis and immunoblot analyses were performed. Both inhibitors attenuated cell proliferation in a dose-dependent manner and induced apoptosis. We found that most of the glioblastoma cells migrated preferentially in an anodal direction, while brain metastases cells were unaffected by direct current stimulations. Afatinib presented only a mild attenuation of galvanotaxis. In contrast, capivasertib abolished the migration of glioblastoma cells without genetic alterations in the PI3K/AKT pathway, but not in cells harboring PTEN mutation. In these cells, an increase in the activation of ERK1/2 may in part substitute the inhibition of the AKT pathway. Overall, our data demonstrate that glioblastoma cells migrate in the electrical field and the PI3K/AKT pathway was found to be highly involved in galvanotaxis.

Collagen Matrices Mediate Glioma Cell Migration Induced by an Electrical Signal

“…Although these studies observed the different responses of the glial cells and neuronal cells to the applied EF stimulation, the mechanism that controls the migration direction of the cells is not clear. A previous study showed that the glioma cell migration can be guided to move toward the anodal pole on a 2D cell culture dish [ 14 , 30 ]. Interestingly, glioma originates from glial cells, and astrocytes and glioma cells all showed anodal migration.…”

Harnessing the Stem Cell Niche in Regenerative Medicine: Innovative Avenue to Combat Neurodegenerative Diseases

“…Endogenous bioelectric fields can dictate cell migration patterns, a phenomenon known as galvanotaxis or electrotaxis [112][113][114]. These fields can influence the movement and localization of stem cells within the niche or modulate their homing capabilities post-transplantation [115][116][117]. Within the niche, endogenous bioelectric gradients may serve as spatiotemporal guides for stem cell differentiation.…”

Biophysical control of plasticity and patterning in regeneration and cancer

“…To model electrotaxis in vitro, there is a growing number of researchers developing devices to generate electric fields to modulate tissue dynamics [ 288 ]. While it is well established that electric fields can drive migration of many different cell types [ 289 , 290 ], the latest data indicate that EM field stimulation at low (30–300 kHz) and extremely low (3–30 Hz) frequencies can modulate the fate and behavior of stem cells including effects on proliferation, differentiation, cell cycle progression, viability, morphology, and metabolism [ 291 ].…”