Nicotinamide phosphoribosyltransferase (NAMPT/PBEF/visfatin) is a tumoural cytokine released from melanoma

Summary 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 melanom...

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Vydáno v:	Pigment cell and melanoma research Ročník 28; číslo 6; s. 718 - 729
Hlavní autoři:	Grolla, Ambra A., Torretta, Simone, Gnemmi, Ilaria, Amoruso, Angela, Orsomando, Giuseppe, Gatti, Marco, Caldarelli, Antonio, Lim, Dmitry, Penengo, Lorenza, Brunelleschi, Sandra, Genazzani, Armando A., Travelli, Cristina
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	England Blackwell Publishing Ltd 01.11.2015 Wiley Subscription Services, Inc
Témata:	Animals Autocrine Communication - drug effects Cell Hypoxia - drug effects Cell Line, Tumor cytokine Cytokines - blood Cytokines - metabolism Extracellular Space - enzymology Humans Hydrogen Peroxide - pharmacology Melanoma Melanoma - enzymology Melanoma - pathology Metabolic disorders Mice, Inbred C57BL Monocytes - drug effects Monocytes - metabolism NAD Nicotinamide phosphoribosyltransferase Nicotinamide Phosphoribosyltransferase - blood Nicotinamide Phosphoribosyltransferase - metabolism Paracrine Communication - drug effects Secretory Vesicles - metabolism Skin Neoplasms - enzymology Skin Neoplasms - pathology Tumors visfatin NAD cytokine melanoma Nicotinamide phosphoribosyltransferase visfatin
ISSN:	1755-1471, 1755-148X
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Shrnutí:	Summary 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.
Bibliografie:	ark:/67375/WNG-KCC2NN0N-S Fondazione San Paolo to ArmAG ArticleID:PCMR12420 Figure S1. Cell viability assay.Figure S2. eNAMPT is released by cancer cell lines of different origin.Figure S3. Cell viability assay.Figure S4. Cell viability assay.Figure S5. Enzymatic activity of the recombinant eNAMPTs used.Figure S6. NAMPT levels.Figure S7. Immunoprecipitation of FLAG-NAMPT in the medium of B16 FLAG-NAMPT cells.Figure S8. Characterization of B16 shNAMPTLow cells explanted from melanoma-bearing mice.Appendix S1. Supporting methods. Associazione Italiana per la Ricerca sul Cancro - No. IG10509 SIF-Takeda istex:E44B8C1B5ACF4DA132854DB551B2CFD8C6DC96E4 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1755-1471 1755-148X
DOI:	10.1111/pcmr.12420