title: 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.
authors.affiliation: Department of Physiology, James H. Quillen College of Medicine, East Tennessee State University, P.O. Box 70,576, Johnson City, TN 37614-1708, USA. wonderge@etsu.edu
authors.forename: Robert
authors.initials: R
authors.lastname: Wondergem
authors.forename: Tom W
authors.initials: TW
authors.lastname: Ecay
authors.forename: Frank
authors.initials: F
authors.lastname: Mahieu
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Owsianik
authors.forename: Bernd
authors.initials: B
authors.lastname: Nilius
mesh_terms: D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D016543:Central Nervous System Neoplasms / Q000378:metabolism / Q000473:pathology*; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology*; D017228:Hepatocyte Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008610:Menthol / Q000633:toxicity*; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D050053:TRPM Cation Channels / Q000819:agonists / Q000235:genetics / Q000378:metabolism*
chemical_list: D001896:Boron Compounds; C066855:HGF protein, human; D012333:RNA, Messenger; D050053:TRPM Cation Channels; C425966:TRPM8 protein, human; D008610:Menthol; D017228:Hepatocyte Growth Factor; C109986:2-aminoethoxydiphenyl borate; D002118:Calcium