title: NAADP-Dependent Ca(2+) Signaling Controls Melanoma Progression, Metastatic Dissemination and Neoangiogenesis.
abstract: A novel transduction pathway for the powerful angiogenic factor VEGF has been recently shown in endothelial cells to operate through NAADP-controlled intracellular release of Ca(2+). In the present report the possible involvement of NAADP-controlled Ca(2+) signaling in tumor vascularization, growth and metastatic dissemination was investigated in a murine model of VEGF-secreting melanoma. Mice implanted with B16 melanoma cells were treated with NAADP inhibitor Ned-19 every second day for 4 weeks and tumor growth, vascularization and metastatization were evaluated. Control specimens developed well vascularized tumors and lung metastases, whereas in Ned-19-treated mice tumor growth and vascularization as well as lung metastases were strongly inhibited. In vitro experiments showed that Ned-19 treatment controls the growth of B16 cells in vitro, their migratory ability, adhesive properties and VEGFR2 expression, indicating NAADP involvement in intercellular autocrine signaling. To this regard, Ca(2+) imaging experiments showed that the response of B16 cells to VEGF stimulation is NAADP-dependent. The whole of these observations indicate that NAADP-controlled Ca(2+) signaling can be relevant not only for neoangiogenesis but also for direct control of tumor cells.
authors.affiliation: Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology,SAPIENZA University of Rome, 16 Via A. Scarpa, 00161 Rome, Italy.
authors.forename: Annarita
authors.initials: A
authors.lastname: Favia
authors.affiliation: Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology,SAPIENZA University of Rome, 16 Via A. Scarpa, 00161 Rome, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Pafumi
authors.affiliation: Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, 53 Via E. Chianesi, 00144, Rome, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Desideri
authors.affiliation: Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology,SAPIENZA University of Rome, 16 Via A. Scarpa, 00161 Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Padula
authors.affiliation: Department of Chemistry, SAPIENZA University of Rome, 5 Piazzale Aldo Moro, 00185 Rome, Italy.
authors.forename: Camilla
authors.initials: C
authors.lastname: Montesano
authors.affiliation: Department of Biomedicine and Prevention, Tor Vergata University of Rome, Via di Tor Vegata, 00173 Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Passeri
authors.affiliation: Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology,SAPIENZA University of Rome, 16 Via A. Scarpa, 00161 Rome, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Nicoletti
authors.affiliation: Department of Biomedicine and Prevention, Tor Vergata University of Rome, Via di Tor Vegata, 00173 Rome, Italy.
authors.forename: Augusto
authors.initials: A
authors.lastname: Orlandi
authors.affiliation: Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, 53 Via E. Chianesi, 00144, Rome, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Del Bufalo
authors.affiliation: Faculty of Biosciences and Technologies for Food, Agriculture and Environment, University of Teramo, 1 Via R. Balzarini, 64023 Teramo, Italy.
authors.forename: Manuel
authors.initials: M
authors.lastname: Sergi
authors.affiliation: Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology,SAPIENZA University of Rome, 16 Via A. Scarpa, 00161 Rome, Italy.
authors.forename: Elio
authors.initials: E
authors.lastname: Ziparo
authors.affiliation: Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology,SAPIENZA University of Rome, 16 Via A. Scarpa, 00161 Rome, Italy.
authors.forename: Fioretta
authors.initials: F
authors.lastname: Palombi
authors.affiliation: Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology,SAPIENZA University of Rome, 16 Via A. Scarpa, 00161 Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Filippini
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002243:Carbolines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D015870:Gene Expression; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008546:Melanoma, Experimental; D051379:Mice; D009249:NADP / Q000031:analogs & derivatives* / Q000378:metabolism; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism*; D010879:Piperazines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity; D047368:Tumor Burden / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
chemical_list: C539827:1-(3-((4-(2-fluorophenyl)piperazin-1-yl)methyl)-4-methoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido(3,4-b)indole-3-carboxylic acid; D002243:Carbolines; D010879:Piperazines; D042461:Vascular Endothelial Growth Factor A; D009249:NADP; C024376:NAADP; D040301:Vascular Endothelial Growth Factor Receptor-2