Blocking glutamate-mediated signalling inhibits human melanoma growth and migration

• Published in: Experimental dermatology 2012-12, Vol.21 (12), p.926-931
• Main Authors: Song, Zhiqi, He, Chun-Di, Liu, Jing, Sun, Changkai, Lu, Ping, Li, Lili, Gao, Lili, Zhang, Yi, Xu, Yanni, Shan, Lujuan, Liu, Yuejian, Zou, Wei, Zhang, Yuan, Gao, Haiqin, Gao, Wenting
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Movement - drug effects; Cell Movement - physiology; Cell Proliferation - drug effects; Chromones - pharmacology; Dermatology; Dizocilpine Maleate - pharmacology; Excitatory Amino Acid Antagonists - pharmacology; Female; Glutamic Acid - metabolism; HEK293 Cells; Humans; MAP2a; Medical sciences; melanoma; Melanoma - drug therapy; Melanoma - metabolism; Melanoma - pathology; mGluR1; Mice; Mice, Inbred BALB C; Mice, Nude; Microtubule-Associated Proteins - metabolism; Microtubules - drug effects; Microtubules - metabolism; N-methyl-d-aspartate receptors; Neoplasm Invasiveness - pathology; Receptors, Metabotropic Glutamate - antagonists & inhibitors; Receptors, Metabotropic Glutamate - metabolism; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - metabolism; Signal Transduction - drug effects; Signal Transduction - physiology; Skin Neoplasms - drug therapy; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; Tumorigenesis; Tumors of the skin and soft tissue. Premalignant lesions; Xenograft Model Antitumor Assays
• ISSN: 0906-6705; 1600-0625
• DOI: 10.1111/exd.12048

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.