Electrotaxis of Glioblastoma and Medulloblastoma Spheroidal Aggregates

Area of Science:

• Oncology
• Cell Biology
• Biophysics

Background:

• Neuroepithelial cancers, including glioblastoma and medulloblastoma, present significant treatment challenges due to invasive growth into critical brain regions.
• Limited accessibility and dispersed tumor cells hinder effective therapeutic strategies for brain tumors.
• Electrotaxis, the directed migration of cells in response to an electrical field, offers a potential avenue for manipulating tumor cell movement.

Purpose of the Study:

• To investigate the phenomenon of electrotaxis in glioblastoma (U87mg) and medulloblastoma (DAOY) cell lines.
• To identify molecular pathways involved in tumor cell electrotaxis using RNA-sequencing and pharmacological inhibition.
• To determine if the PI3K/mTOR/AKT signaling axis causally influences electrotactic responses in these brain tumor cells.

Main Methods:

• Cultured U87mg and DAOY brain cancer cell lines as spheroidal aggregates.
• Utilized Matrigel-filled electrotaxis channels to apply direct-current electrical fields.
• Performed RNA-sequencing for pathway discovery and selective pharmacological inhibition assays targeting the PI3K/mTOR/AKT signaling axis.

Main Results:

• Observed opposing electrotactic responses between U87mg and DAOY cell lines.
• RNA-sequencing identified differentially affected signaling pathways upon exposure to electrical fields.
• Pharmacological inhibition of PI3Kγ, mTOR, AKT, and ErbB2 abolished U87mg cell electrotaxis, while DAOY cell electrotaxis remained unaffected by these inhibitors.

Conclusions:

• Brain tumor cells exhibit distinct electrotactic behaviors.
• The PI3K/mTOR/AKT and ErbB2 signaling pathways are crucial for U87mg glioblastoma cell electrotaxis.
• DAOY medulloblastoma cell electrotaxis appears to be regulated by different, yet uncharacterized, mechanisms.