title: Nicotinamide phosphoribosyltransferase (NAMPT/PBEF/visfatin) is a tumoural cytokine released from melanoma.
abstract: High plasma levels of nicotinamide phosphoribosyltransferase (NAMPT), traditionally considered an intracellular enzyme with a key role in NAD synthesis, have been reported in several oncological, inflammatory and metabolic diseases. We now show that eNAMPT can be actively released by melanoma cells in vitro. We analysed the mechanisms of its release, and we found both classical and non-classical pathway involvement. eNAMPT released by melanoma cells, in our hands, has paracrine and autocrine effects: it activates MAPK, AKT and NF-κB pathways and increases colony formation in anchorage-independent conditions. eNAMPT also induces M1 polarization in human monocytes. Last, we demonstrate, for the first time in any cancer type, that eNAMPT levels in plasma of tumour-bearing mice increase and that this increase can be reconducted to the tumour itself. This provides an important cue on previous observations that eNAMPT is increased in patients with cancer. Moreover, silencing NAMPT in melanoma cells leads to a reduction in the tumour growth rate. Our findings extend the basis to consider eNAMPT as a cytokine involved in tumour progression.
authors.affiliation: Department of Pharmaceutical Sciences and Department of Medical Sciences, Università del Piemonte Orientale, Novara, Italy.
authors.forename: Ambra A
authors.initials: AA
authors.lastname: Grolla
authors.affiliation: Department of Pharmaceutical Sciences and Department of Medical Sciences, Università del Piemonte Orientale, Novara, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Torretta
authors.affiliation: Department of Pharmaceutical Sciences and Department of Medical Sciences, Università del Piemonte Orientale, Novara, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Gnemmi
authors.affiliation: Department of Pharmaceutical Sciences and Department of Medical Sciences, Università del Piemonte Orientale, Novara, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Amoruso
authors.affiliation: Section of Biochemistry, Department of Clinical Sciences, Polytechnic University of Marche, Ancona, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Orsomando
authors.affiliation: Department of Pharmaceutical Sciences and Department of Medical Sciences, Università del Piemonte Orientale, Novara, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Gatti
authors.affiliation: Department of Pharmaceutical Sciences and Department of Medical Sciences, Università del Piemonte Orientale, Novara, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Caldarelli
authors.affiliation: Department of Pharmaceutical Sciences and Department of Medical Sciences, Università del Piemonte Orientale, Novara, Italy.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Lim
authors.affiliation: Department of Pharmaceutical Sciences and Department of Medical Sciences, Università del Piemonte Orientale, Novara, Italy.|Institute of Pharmacology and Toxicology, University of Zürich-Vetsuisse, Zürich, Switzerland.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Penengo
authors.affiliation: Department of Pharmaceutical Sciences and Department of Medical Sciences, Università del Piemonte Orientale, Novara, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Brunelleschi
authors.affiliation: Department of Pharmaceutical Sciences and Department of Medical Sciences, Università del Piemonte Orientale, Novara, Italy.
authors.forename: Armando A
authors.initials: AA
authors.lastname: Genazzani
authors.affiliation: Department of Pharmaceutical Sciences and Department of Medical Sciences, Università del Piemonte Orientale, Novara, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Travelli
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D045744:Cell Line, Tumor; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D005110:Extracellular Space / Q000201:enzymology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008545:Melanoma / Q000201:enzymology* / Q000473:pathology; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D054409:Nicotinamide Phosphoribosyltransferase / Q000097:blood / Q000378:metabolism*; D019899:Paracrine Communication / Q000187:drug effects; D022142:Secretory Vesicles / Q000378:metabolism; D012878:Skin Neoplasms / Q000201:enzymology* / Q000473:pathology
chemical_list: D016207:Cytokines; D006861:Hydrogen Peroxide; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human
keywords: NAD; Nicotinamide phosphoribosyltransferase; cytokine; melanoma; visfatin