Effects of Galectin-3 inhibitors paired with direct current stimulation in preclinical models of aggressive meningioma.

Purpose Galectin-3 (Gal-3), a multifunctional β-galactoside-binding lectin, is more highly expressed in atypical and anaplastic meningioma subtypes than in normal brain tissue. The mechanism(s) by which Gal-3 may contribute to the aggressive growth of these tumors remains unclear. Methods We evaluated the effects of the Gal-3 inhibitor TD139 combined with either low-intensity direct current electrostimulation (DCES) on meningioma cells in a human co-culture model, or non-invasive transcranial direct current stimulation (tDCS) in an orthotopic preclinical model. Results In vitro, DCES treatment modulated the expression of human leukocyte antigen (HLA) class I and II molecules, which may influence T cell-tumor cell interactions. Gal-3 was found to activate microglia and promote the differentiation of CD4(+) T cells toward Th2 and Treg phenotypes. Treatment with an immunomodulatory dose of DCES, followed by TD139, induced anaplastic meningioma cell death in a human co-culture model without affecting neurons. In the orthotopic allograft preclinical model, treatment with TD139 and tDCS, administered 7 times over 14 days, significantly reduced tumor growth. Survival of tumor-bearing mice treated with TD139 and tDCS was significantly higher than that of untreated controls or mice treated with tDCS or TD139 alone. This combination treatment was also associated with a significant decrease in the meningioma-associated marker NDRG4 and the proliferation marker Ki-67. Conclusion The results indicate that combining Gal-3 inhibitors with direct current stimulation has potential as an effective treatment modality for aggressive meningiomas.