title: Osteosarcoma cell proliferation and survival requires mGluR5 receptor activity and is blocked by Riluzole.
abstract: Osteosarcomas are malignant tumors of bone, most commonly seen in children and adolescents. Despite advances in modern medicine, the poor survival rate of metastatic osteosarcoma has not improved in two decades. In the present study we have investigated the effect of Riluzole on a human and mouse metastatic osteosarcoma cells. We show that LM7 cells secrete glutamate in the media and that mGluR5 receptors are required for the proliferation of LM7 cells. Riluzole, which is known to inhibit glutamate release, inhibits proliferation, induces apoptosis and prevents migration of LM7 cells. This is also seen with Fenobam, a specific blocker of mGluR5. We also show that Riluzole alters the phosphorylation status of AKT/P70 S6 kinase, ERK1/2 and JNK1/2. Thus Riluzole is an effective drug to inhibit proliferation and survival of osteosarcoma cells and has therapeutic potential for the treatment of osteosarcoma exhibiting autocrine glutamate signaling.
authors.affiliation: Department of Medical Laboratory Sciences, Hunter College, City University of New York, New York, NY, United States of America.
authors.forename: Sally
authors.initials: S
authors.lastname: Liao
authors.affiliation: Department of Medical Laboratory Sciences, Hunter College, City University of New York, New York, NY, United States of America.
authors.forename: Yuleisy
authors.initials: Y
authors.lastname: Ruiz
authors.affiliation: Department of Medical Laboratory Sciences, Hunter College, City University of New York, New York, NY, United States of America.
authors.forename: Hira
authors.initials: H
authors.lastname: Gulzar
authors.affiliation: Department of Medical Laboratory Sciences, Hunter College, City University of New York, New York, NY, United States of America.
authors.forename: Zarina
authors.initials: Z
authors.lastname: Yelskaya
authors.affiliation: Department of Medical Laboratory Sciences, Hunter College, City University of New York, New York, NY, United States of America.
authors.forename: Lyes
authors.initials: L
authors.lastname: Ait Taouit
authors.affiliation: Department of Medical Laboratory Sciences, Hunter College, City University of New York, New York, NY, United States of America.
authors.forename: Murielle
authors.initials: M
authors.lastname: Houssou
authors.affiliation: Department of Medical Laboratory Sciences, Hunter College, City University of New York, New York, NY, United States of America.
authors.forename: Trisha
authors.initials: T
authors.lastname: Jaikaran
authors.affiliation: Department of Medical Laboratory Sciences, Hunter College, City University of New York, New York, NY, United States of America.
authors.forename: Yuriy
authors.initials: Y
authors.lastname: Schvarts
authors.affiliation: Department of Medical Laboratory Sciences, Hunter College, City University of New York, New York, NY, United States of America.
authors.forename: Kristina
authors.initials: K
authors.lastname: Kozlitina
authors.affiliation: Department of Microbiology & Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY, United States of America.
authors.forename: Upal
authors.initials: U
authors.lastname: Basu-Roy
authors.affiliation: Department of Microbiology & Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY, United States of America.
authors.forename: Alka
authors.initials: A
authors.lastname: Mansukhani
authors.affiliation: Department of Medical Laboratory Sciences, Hunter College, City University of New York, New York, NY, United States of America.|Brain and Mind Research Institute, Weil Cornell Medical College, New York, NY, United States of America.
authors.forename: Shahana S
authors.initials: SS
authors.lastname: Mahajan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D051379:Mice; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D064529:Receptor, Metabotropic Glutamate 5 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019782:Riluzole / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D018691:Excitatory Amino Acid Antagonists; D064529:Receptor, Metabotropic Glutamate 5; D018698:Glutamic Acid; D019782:Riluzole