title: Adiponectin as novel regulator of cell proliferation in human glioblastoma.
abstract: Adiponectin (Acrp30) is an adipocyte-secreted hormone with pleiotropic metabolic effects, whose reduced levels were related to development and progression of several malignancies. We looked at the presence of Acrp30 receptors in human glioblastomas (GBM), hypothesizing a role for Acrp30 also in this untreatable cancer. Here we demonstrate that human GBM express Acrp30 receptors (AdipoR1 and AdipoR2), which are often co-expressed in GBM samples (70% of the analyzed tumors). To investigate the effects of Acrp30 on GBM growth, we used human GBM cell lines U87-MG and U251, expressing both AdipoR1 and AdipoR2 receptors. In these cells, Acrp30 treatment inhibits DNA synthesis and cell proliferation rate, inducing arrest in G1 phase of the cell cycle. These effects were correlated to a sustained activation of ERK1/2 and Akt kinases, upon Acrp30 treatment. Our results suggest that Acrp30 may represent a novel endogenous negative regulator of GBM cell proliferation, to be evaluated for the possible development of novel pharmacological approaches.
authors.affiliation: Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy.
authors.forename: Carola
authors.initials: C
authors.lastname: Porcile
authors.forename: Erika
authors.initials: E
authors.lastname: Di Zazzo
authors.forename: Maria Ludovica
authors.initials: ML
authors.lastname: Monaco
authors.forename: Giorgia
authors.initials: G
authors.lastname: D'Angelo
authors.forename: Daniela
authors.initials: D
authors.lastname: Passarella
authors.forename: Claudio
authors.initials: C
authors.lastname: Russo
authors.forename: Alfonso
authors.initials: A
authors.lastname: Di Costanzo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pattarozzi
authors.forename: Monica
authors.initials: M
authors.lastname: Gatti
authors.forename: Adriana
authors.initials: A
authors.lastname: Bajetto
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Zona
authors.forename: Federica
authors.initials: F
authors.lastname: Barbieri
authors.forename: Giovannangelo
authors.initials: G
authors.lastname: Oriani
authors.forename: Bruno
authors.initials: B
authors.lastname: Moncharmont
authors.forename: Tullio
authors.initials: T
authors.lastname: Florio
authors.forename: Aurora
authors.initials: A
authors.lastname: Daniele
mesh_terms: D052242:Adiponectin / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D054419:Receptors, Adiponectin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors
chemical_list: C499918:ADIPOQ protein, human; C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D000970:Antineoplastic Agents; D054419:Receptors, Adiponectin; D051057:Proto-Oncogene Proteins c-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3