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AuthorCecchi, Marta
AuthorMannini, Antonella
AuthorLapucci, Andrea
AuthorSilvano, Angela
AuthorLulli, Matteo
AuthorLuceri, Cristina
AuthorD’Ambrosio, Mario
AuthorChiarugi, Alberto
AuthorEid, Ali H.
AuthorParenti, Astrid
Available date2023-01-30T06:43:51Z
Publication Date2022-06-30
Publication NameFrontiers in Pharmacology
Identifierhttp://dx.doi.org/10.3389/fphar.2022.911019
CitationCecchi M, Mannini A, Lapucci A, Silvano A, Lulli M, Luceri C, D’Ambrosio M, Chiarugi A, Eid AH and Parenti A (2022) Dexamethasone Promotes a Stem-Like Phenotype in Human Melanoma Cells via Tryptophan 2,3 Dioxygenase. Front. Pharmacol. 13:911019. doi: 10.3389/fphar.2022.911019
URIhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85134257829&origin=inward
URIhttp://hdl.handle.net/10576/39170
AbstractIn addition to its well-established immunosuppressive actions, tryptophan 2,3-dioxygenase (TDO) appears to elicit direct effects on tumor cell function. Although TDO has been associated with cancer stemness, its involvement in melanoma stem cell biology remains largely unknown. Since we showed that by upregulating TDO, dexamethasone (dex) promotes proliferation and migration of SK-Mel-28 human melanoma cells, we sought to investigate dex effects on melanoma spherogenesis and stemness, and whether these events are mediated by TDO. We demonstrate here that dex significantly upregulates TDO in A375, a more aggressive melanoma cell line, confirming that dex effects are not limited to SK-Mel-28 cells. Moreover, dex stimulates spherogenesis of both cell lines, which is mediated by TDO, evident by its suppression with 680C91, a TDO inhibitor. The formed melanospheres appear to be enriched with embryonic stem cell marker mRNAs, the expression of which is potentiated by dex. Expression of cancer stem cell markers (CD133, CD44, ganglioside GD2) was significantly increased in A375 spheres, as detected by flow cytometry. Taken together, our results suggest that TDO could represent a promising target in the management of melanoma and that dex, routinely used as a co-medication also in advanced melanoma, may stimulate melanoma cell function/tumor-supporting properties, a rather debilitating and undesired side effect.
SponsorThis work was supported by grants from the University of Florence (RICATEN, Research funding UNIFI) to AP and from Tuscany Region Health Project 2018 (Bando Ricerca Salute 2018–ANTI NCT) to AC. Open Access funding provided by Qatar National Library.
Languageen
PublisherFrontiers Media
SubjectA375
dexamethasone
embryonic stem cell markers
glucocorticoids
melanoma
melanospheres
SK-MEL-28
tryptophan 2,3 dioxygenase
TitleDexamethasone Promotes a Stem-Like Phenotype in Human Melanoma Cells via Tryptophan 2,3 Dioxygenase
TypeArticle
Volume Number13
ESSN1663-9812
dc.accessType Open Access


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