Dexamethasone Promotes a Stem-Like Phenotype in Human Melanoma Cells <i>via</i> Tryptophan 2,3 Dioxygenase
<p dir="ltr">In 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 u...
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| مؤلفون آخرون: | , , , , , , , , |
| منشور في: |
2022
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| _version_ | 1864513548254707712 |
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| author | Marta Cecchi (21363581) |
| author2 | Antonella Mannini (21363584) Andrea Lapucci (470257) Angela Silvano (21363587) Matteo Lulli (7463885) Cristina Luceri (3567536) Mario D’Ambrosio (13172607) Alberto Chiarugi (321191) Ali H. Eid (5461829) Astrid Parenti (578664) |
| author2_role | author author author author author author author author author |
| author_facet | Marta Cecchi (21363581) Antonella Mannini (21363584) Andrea Lapucci (470257) Angela Silvano (21363587) Matteo Lulli (7463885) Cristina Luceri (3567536) Mario D’Ambrosio (13172607) Alberto Chiarugi (321191) Ali H. Eid (5461829) Astrid Parenti (578664) |
| author_role | author |
| dc.creator.none.fl_str_mv | Marta Cecchi (21363581) Antonella Mannini (21363584) Andrea Lapucci (470257) Angela Silvano (21363587) Matteo Lulli (7463885) Cristina Luceri (3567536) Mario D’Ambrosio (13172607) Alberto Chiarugi (321191) Ali H. Eid (5461829) Astrid Parenti (578664) |
| dc.date.none.fl_str_mv | 2022-06-30T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3389/fphar.2022.911019 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Dexamethasone_Promotes_a_Stem-Like_Phenotype_in_Human_Melanoma_Cells_i_via_i_Tryptophan_2_3_Dioxygenase/29069585 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Immunology Oncology and carcinogenesis Pharmacology and pharmaceutical sciences melanoma, SK-MEL-28 A375 dexamethasone glucocorticoids tryptophan 2,3 dioxygenase melanospheres embryonic stem cell markers |
| dc.title.none.fl_str_mv | Dexamethasone Promotes a Stem-Like Phenotype in Human Melanoma Cells <i>via</i> Tryptophan 2,3 Dioxygenase |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">In 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.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Pharmacology<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fphar.2022.911019" target="_blank">https://dx.doi.org/10.3389/fphar.2022.911019</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_c0e7beb7059c2cbc392b6ef0b924b702 |
| identifier_str_mv | 10.3389/fphar.2022.911019 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/29069585 |
| publishDate | 2022 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Dexamethasone Promotes a Stem-Like Phenotype in Human Melanoma Cells <i>via</i> Tryptophan 2,3 DioxygenaseMarta Cecchi (21363581)Antonella Mannini (21363584)Andrea Lapucci (470257)Angela Silvano (21363587)Matteo Lulli (7463885)Cristina Luceri (3567536)Mario D’Ambrosio (13172607)Alberto Chiarugi (321191)Ali H. Eid (5461829)Astrid Parenti (578664)Biomedical and clinical sciencesImmunologyOncology and carcinogenesisPharmacology and pharmaceutical sciencesmelanoma,SK-MEL-28A375dexamethasoneglucocorticoidstryptophan 2,3 dioxygenasemelanospheresembryonic stem cell markers<p dir="ltr">In 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.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Pharmacology<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fphar.2022.911019" target="_blank">https://dx.doi.org/10.3389/fphar.2022.911019</a></p>2022-06-30T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3389/fphar.2022.911019https://figshare.com/articles/journal_contribution/Dexamethasone_Promotes_a_Stem-Like_Phenotype_in_Human_Melanoma_Cells_i_via_i_Tryptophan_2_3_Dioxygenase/29069585CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/290695852022-06-30T09:00:00Z |
| spellingShingle | Dexamethasone Promotes a Stem-Like Phenotype in Human Melanoma Cells <i>via</i> Tryptophan 2,3 Dioxygenase Marta Cecchi (21363581) Biomedical and clinical sciences Immunology Oncology and carcinogenesis Pharmacology and pharmaceutical sciences melanoma, SK-MEL-28 A375 dexamethasone glucocorticoids tryptophan 2,3 dioxygenase melanospheres embryonic stem cell markers |
| status_str | publishedVersion |
| title | Dexamethasone Promotes a Stem-Like Phenotype in Human Melanoma Cells <i>via</i> Tryptophan 2,3 Dioxygenase |
| title_full | Dexamethasone Promotes a Stem-Like Phenotype in Human Melanoma Cells <i>via</i> Tryptophan 2,3 Dioxygenase |
| title_fullStr | Dexamethasone Promotes a Stem-Like Phenotype in Human Melanoma Cells <i>via</i> Tryptophan 2,3 Dioxygenase |
| title_full_unstemmed | Dexamethasone Promotes a Stem-Like Phenotype in Human Melanoma Cells <i>via</i> Tryptophan 2,3 Dioxygenase |
| title_short | Dexamethasone Promotes a Stem-Like Phenotype in Human Melanoma Cells <i>via</i> Tryptophan 2,3 Dioxygenase |
| title_sort | Dexamethasone Promotes a Stem-Like Phenotype in Human Melanoma Cells <i>via</i> Tryptophan 2,3 Dioxygenase |
| topic | Biomedical and clinical sciences Immunology Oncology and carcinogenesis Pharmacology and pharmaceutical sciences melanoma, SK-MEL-28 A375 dexamethasone glucocorticoids tryptophan 2,3 dioxygenase melanospheres embryonic stem cell markers |