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

Abstract

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.

Benzoquinone ansamycin 17AAG binds to mitochondrial voltage-dependent anion channel and inhibits cell invasion

“…To test whether the increase in [Ca 2+ ] i by GA and Ub0 occurred by SOCE, we performed whole-cell voltage clamp measurements on both MDCK and DBTRG cells to measure the nonselective cationic current. HGF/SF treatment increased this current (Table 1), consistent with previous findings (23,24). Dramatically, GA at picomolar levels inhibited cationic currents within 6 min after addition to either MDCK or DBTRG cells (Table 1 and Figs.…”

Blockade of TRPM8 activity reduces the invasion potential of oral squamous carcinoma cell lines

“…Stimulation with menthol has been shown to increase both the intracellular Ca 2+ level and cell migration in human glioblastoma cells (25,26). The present results demonstrated that in the two HSC cell lines, menthol augmented motility, while RQ inhibited it through blockade of menthol-induced and constitutive TRPM8 activities, although neither of these agents had any effect on cell proliferation.…”

Ionic Channels in the Therapy of Malignant Glioma

“…In DBTRG glioblastoma cells, menthol could activate Ca 2+ entry and promote cell migration, and TRPM8 channels were found to mediate menthol-induced intracellular Ca 2+ elevation and cell migration, suggesting that Ca 2+ influx via TRPM8 is necessary for glioma cell migration in response to menthol stimuli (Wondergem et al, 2008).…”