Dexamethasone Promotes a Stem-Like Phenotype in Human Melanoma Cells via Tryptophan 2,3 Dioxygenase

Cecchi, Matteo; Mannini, Antonella; Lapucci, Andrea; Silvano, Angela; Lulli, Matteo; Luceri, Cristina; D’Ambrosio, Mario; Chiarugi, Alberto; Eid, Ali H.; Parenti, Astrid

doi:10.3389/fphar.2022.911019

Cited by 4 publications

(4 citation statements)

References 54 publications

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“…The A375 cell line was obtained from the Department of Dermatology, Xiangya Hospital, Central South University, and cultured as previously described 31 . Clinical samples were collected from The Affiliated Cancer Hospital of Xiangya School of Medicine, with a total of 24 cases of melanoma and 8 cases of normal tissues.…”

Section: Methodsmentioning

confidence: 99%

TNFSF10, an autophagy related gene, was a prognostic and immune infiltration marker in skin cutaneous melanoma

Li¹,

Zhang²,

Ju³

et al. 2023

J. Cancer

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Autophagy exerts a pivotal effect on skin cutaneous melanoma (SKCM). This study was aimed to investigate the expression of autophagy related genes (ARGs) in SKCM as well as its clinical value. Differentially expressed (DE) ARGs were downloaded from the intersection of SKCM data in GEPIA2 database and ARGs in Human Autophagy Database (HADB) database, and were verified in SKCM datasets GSE46517 and GSE15605. DE ARGs were enriched by Metascape online tools. According to GEPIA2 database, tumor necrosis factor-related apoptosis-inducing ligand (TNFSF10) was identified as a closely related factor and prognostic marker of SKCM. Then the correlation analysis of clinicopathological characteristics between TNFSF10 and SKCM was completed by several online tools such as TISCH, HPA, BEST and qRT-PCR. Subsequently, we investigated TNFSF10 related functions and signal pathways with LinkedOmics online tool, and immune infiltration using Assistant for Clinical Bioinformatics online tool. Furthermore, correlation analysis between TNFSF10 expression and immunotherapy response was performed by TIDE algorithm and BEST online tool. And Kaplan-Meier Plotter was used to assessing the prognosis of SKCM patients receiving immunotherapy. Finally, the correlation analysis among TNFSF10 methylation, TNFSF10 expression and patient prognosis was completed by the DiseaseMeth version 2.0, UCSC XENA and qRT-PCR. ARGs are DE in SKCM and participate in the ERBB signaling pathway, as well as the processing and presentation of antigens. Moreover, TNFSF10's expression along with methylation expression were significantly associated with the prognosis. Low expression of TNFSF10 was associated with malignant clinicopathological features, lower immune signal activity and lower immunocytes abundance in patients with SKCM. As an ARG, TNFSF10 has a potential capacity in predicting the prognosis of SKCM patients, meanwhile, may be a novel immunotherapy marker for SKCM.

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Section: Methodsmentioning

confidence: 99%

TNFSF10, an autophagy related gene, was a prognostic and immune infiltration marker in skin cutaneous melanoma

Li¹,

Zhang²,

Ju³

et al. 2023

J. Cancer

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“…Total RNA was isolated using TRI Reagent and spectroscopically quantified by Nan-oDrop (ThermoFisher Scientific, Milan, Italy) instrument. One µg of total RNA was reverse transcribed by means of Prime Script RT reagent Kit with gDNA eraser (Takara, Otsu, Japan), and cDNA was amplified with specific primers described in Cecchi et al [7]. Quantitative real-time PCR (qRT-PCR) was performed by SYBR Premix Ex Taq kit (Takara, Otsu, Japan) according to the manufacturer's instructions using a Rotorgene RG-3000A system (Qiagen, Monza, Italy).…”

Section: Real-time Pcrmentioning

confidence: 99%

“…Recent reports have highlighted TDO's involvement in the progression of some tumors [4,5]. We previously demonstrated that TDO is expressed by two human melanoma cell lines, namely A375 and SK-Mel-28 and regulates their phenotype and function [6,7]. Melanoma growth and metastasis depend on angiogenesis, the process of new capillary formation starting from pre-existing vessels [8].…”

Section: Introductionmentioning

confidence: 99%

Unveiling the Role of Tryptophan 2,3-Dioxygenase in the Angiogenic Process

Cecchi,

Anceschi,

Silvano

et al. 2024

Pharmaceuticals

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Background: Indoleamine 2,3-dioxygenase (IDO1) and tryptophan-2,3-dioxygenase (TDO) are the two principals enzymes involved in the catabolization of tryptophan (Trp) into kynurenine (Kyn). Despite their well-established role in the immune escape, their involvement in angiogenesis remains uncertain. We aimed to characterize TDO and IDO1 in human umbilical venular endothelial cells (HUVECs) and human endothelial colony-forming cells (ECFCs). Methods: qRT-PCR and immunofluorescence were used for TDO and IDO1 expression while their activity was measured using ELISA assays. Cell proliferation was examined via MTT tests and in in vitro angiogenesis by capillary morphogenesis. Results: HUVECs and ECFCs expressed TDO and IDO1. Treatment with the selective TDO inhibitor 680C91 significantly impaired HUVEC proliferation and 3D-tube formation in response to VEGF-A, while IDO1 inhibition showed no effect. VEGF-induced mTor phosphorylation and Kyn production were hindered by 680C91. ECFC morphogenesis was also inhibited by 680C91. Co-culturing HUVECs with A375 induced TDO up-regulation in both cell types, whose inhibition reduced MMP9 activity and prevented c-Myc and E2f1 upregulation. Conclusions: HUVECs and ECFCs express the key enzymes of the kynurenine pathway. Significantly, TDO emerges as a pivotal player in in vitro proliferation and capillary morphogenesis, suggesting a potential pathophysiological role in angiogenesis beyond its well-known immunomodulatory effects.

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“…Studies using HepG2 liver cancer cells demonstrated that TDO2-inhibitors 680C91 or LM10 significantly reduced Trp degradation and that TDO2, but not IDO1, was the primary source of Kyn production in these cells ( 144 ). 680C91 has also been explored in other cancer types including melanoma ( 145 – 147 ), colon ( 147 ), leiomyomas ( 148 ), and gliomas ( 149 ).…”

Section: Targeting the Kynurenine Pathway For Anti-cancer Treatmentmentioning

confidence: 99%

The kynurenine pathway presents multi-faceted metabolic vulnerabilities in cancer

León-Letelier,

Dou,

Vykoukal

et al. 2023

Front. Oncol.

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The kynurenine pathway (KP) and associated catabolites play key roles in promoting tumor progression and modulating the host anti-tumor immune response. To date, considerable focus has been on the role of indoleamine 2,3-dioxygenase 1 (IDO1) and its catabolite, kynurenine (Kyn). However, increasing evidence has demonstrated that downstream KP enzymes and their associated metabolite products can also elicit tumor-microenvironment immune suppression. These advancements in our understanding of the tumor promotive role of the KP have led to the conception of novel therapeutic strategies to target the KP pathway for anti-cancer effects and reversal of immune escape. This review aims to 1) highlight the known biological functions of key enzymes in the KP, and 2) provide a comprehensive overview of existing and emerging therapies aimed at targeting discrete enzymes in the KP for anti-cancer treatment.

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Dexamethasone Promotes a Stem-Like Phenotype in Human Melanoma Cells via Tryptophan 2,3 Dioxygenase

Cited by 4 publications

References 54 publications

TNFSF10, an autophagy related gene, was a prognostic and immune infiltration marker in skin cutaneous melanoma

TNFSF10, an autophagy related gene, was a prognostic and immune infiltration marker in skin cutaneous melanoma

Unveiling the Role of Tryptophan 2,3-Dioxygenase in the Angiogenic Process

The kynurenine pathway presents multi-faceted metabolic vulnerabilities in cancer

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