HGF/SF and menthol increase human glioblastoma cell calcium and migration

This study explored the role of transient receptor potential melastatin 8 ion channels (TRPM8) in mechanisms of human glioblastoma (DBTRG) cell migration. Menthol stimulated influx of Ca 2+, membrane current, and migration of DBTRG cells. Effects on Ca 2+ and migration were enhanced by pre-treatment with hepatocyte growth factor/scatter factor (HGF/SF). Effects on Ca 2+ also were greater in migrating cells compared with non-migrating cells. 2-Aminoethoxydiphenyl borate (2-APB) inhibited all menthol stimulations. RT-PCR and immunoblot analysis showed that DBTRG cells expressed both mRNA and protein for TRPM8 ion channels. Two proteins were evident: one (130–140 kDa) in a plasma membrane-enriched fraction, and a variant (95–100 kDa) in microsome- and plasma membrane-enriched fractions. Thus, TRPM8 plays a role in mechanisms that increase [Ca 2+] i needed for DBTRG cell migration.