title: Insulin-like-growth-factor-binding-protein-3 (IGFBP-3) contrasts melanoma progression in vitro and in vivo.
abstract: Insulin-like-factor-binding-protein 3 (IGFBP-3) is known to modulate the activity of insulin-like growth factors (IGFs) besides having a number of IGF-independent effects on cell growth and survival. IGFBP-3 has been reported to decrease significantly in the blood serum of patients affected by certain cancers. In the present work, we have evaluated the levels of IGFBP-3 in the blood serum and tissues of patients affected by cutaneous melanoma, showing that loss of IGFBP-3 from both is strongly correlated with disease progression and reduced survival. In vitro treatment with IGFBP-3 of human and murine metastatic melanoma cell lines specifically inhibited the cells' migratory and invasive behaviour, inducing up-regulation of melanocytic differentiation markers such as tyrosinase activity and melanin content. A molecular analysis of the cellular pathways transducing the effect of IGFBP-3 implicated the Akt-GSK3β axis. Moreover, administration of IGFBP-3 in vivo to SCID mice inoculated with human metastatic melanoma cells strongly reduced or completely inhibited tumor growth. In summary, IGFBP-3 appears to exert a specific inhibitory effect on melanoma growth and dissemination, suggesting that it may qualify as a useful therapeutic agent in melanomas and perhaps other cancers, at the least as a valid adjuvant therapy during treatment with conventional anti-tumoral drugs.
authors.affiliation: Istituto Pasteur-Fondazione Cenci-Bolognetti, Dpt. Biotecnologie Cellulari ed Ematologia, University of Rome Sapienza, Rome, Italy.
authors.forename: Antimo
authors.initials: A
authors.lastname: Naspi
authors.affiliation: Plastic Surgery Unit, Campus Bio-Medico University of Rome, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Panasiti
authors.affiliation: Istituto Pasteur-Fondazione Cenci-Bolognetti, Dpt. Biotecnologie Cellulari ed Ematologia, University of Rome Sapienza, Rome, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Abbate
authors.affiliation: Department of Internal Medicine and Medical Specialties, University of Rome Sapienza, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Roberti
authors.affiliation: Plastic Surgery Unit, Campus Bio-Medico University of Rome, Rome, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Devirgiliis
authors.affiliation: Department of Internal Medicine and Medical Specialties, University of Rome Sapienza, Rome, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Curzio
authors.affiliation: Department of Therapeutic Research and Medicine Evaluation, Unit of Antitumor Drugs, Istituto Superiore di Sanita', Rome, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Borghi
authors.affiliation: Department of Therapeutic Research and Medicine Evaluation, Unit of Antitumor Drugs, Istituto Superiore di Sanita', Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Lozupone
authors.affiliation: Department of Human Anatomy (CIR), University Campus Bio-Medico of Rome, Rome, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Carotti
authors.affiliation: Department of Human Anatomy (CIR), University Campus Bio-Medico of Rome, Rome, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Morini
authors.affiliation: Department of Human Anatomy, University of Rome Sapienza, Rome, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Gaudio
authors.affiliation: Department of Internal Medicine and Medical Specialties, University of Rome Sapienza, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Calvieri
authors.affiliation: Istituto Pasteur-Fondazione Cenci-Bolognetti, Dpt. Biotecnologie Cellulari ed Ematologia, University of Rome Sapienza, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Londei
mesh_terms: D000328:Adult; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008544:Melanocytes / Q000187:drug effects / Q000473:pathology; D008545:Melanoma / Q000097:blood / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011994:Recombinant Proteins / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D016019:Survival Analysis; D059016:Tumor Microenvironment / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D011994:Recombinant Proteins; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3