title: Blocking glutamate-mediated signalling inhibits human melanoma growth and migration.
abstract: Glutamate is an excitatory neurotransmitter that has been shown to regulate the proliferation, migration and survival of neuronal progenitors in the central nervous system through its action on metabotropic and ionotropic glutamate receptors (GluRs). Antagonists of ionotropic GluRs have been shown to cause a rapid and reversible change in melanocyte dendritic morphology, which is associated with the disorganization of actin and tubulin microfilaments in the cytoskeleton. Intracellular expression of microtubule-associated protein (MAP) 2a affects the assembly, stabilization and bundling of microtubules in melanoma cells; stimulates the development of dendrites; and suppresses melanoma cell migration and invasion. In this study, we investigated the relationship between glutamate-mediated signalling and microtubules, cell dendritic morphology and melanoma cell motility. We found that metabotropic GluR1 and N-methyl-d-aspartate receptor antagonists increased dendritic branching and inhibited the motility, migration and proliferation of melanoma cells. We also demonstrated that the invasion and motility of melanoma cells are significantly inhibited by the combination of increased expression of MAP2a and either metabotropic GluR1 or N-methyl-d-aspartate receptor antagonists. Moreover, the blockade of glutamate receptors inhibited melanoma growth in vivo. Collectively, these results demonstrate the importance of glutamate signalling in human melanoma and suggest that the blockade of glutamate receptors is a promising novel therapy for treating melanoma.
authors.affiliation: Dermatology Department of 1st Affiliated Hospital, Dalian Medical University, Dalian City, Liaoning Province, China. szqdalian@yahoo.com
authors.forename: Zhiqi
authors.initials: Z
authors.lastname: Song
authors.forename: Chun-Di
authors.initials: CD
authors.lastname: He
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Changkai
authors.initials: C
authors.lastname: Sun
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.forename: Lili
authors.initials: L
authors.lastname: Li
authors.forename: Lili
authors.initials: L
authors.lastname: Gao
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yanni
authors.initials: Y
authors.lastname: Xu
authors.forename: Lujuan
authors.initials: L
authors.lastname: Shan
authors.forename: Yuejian
authors.initials: Y
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Zou
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Haiqin
authors.initials: H
authors.lastname: Gao
authors.forename: Wenting
authors.initials: W
authors.lastname: Gao
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D002867:Chromones; D016291:Dizocilpine Maleate; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D008869:Microtubule-Associated Proteins; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C117789:7-(hydroxyimino)cyclopropan(b)chromen-1a-carbxoylic acid ethyl ester; C489788:MAP2 protein, human; C104077:metabotropic glutamate receptor type 1