1-Methyl-D-Tryptophan Potentiates TGF-beta-Induced Epithelial-Mesenchymal Transition in T24 Human Bladder Cancer Cells

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art_BRITO_1MethylDTryptophan_Potentiates_TGFbetaInduced_EpithelialMesenchymal_Transition_in_T24_Human_2015.PDF (8.55 MB)
Citações na Scopus
17
Tipo de produção
article
Data de publicação
2015
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
PUBLIC LIBRARY SCIENCE
Autores
BRITO, Rodrigo Barbosa Oliveira
MALTA, Camila Soares
SOUZA, Diego Mota
MATHEUS, Luiz Henrique Gomes
MATOS, Yves Silva Teles
SILVA, Chrisna Souza
FERREIRA, Janaina Mendes
FRANCA, Cristiane Miranda
DELLE, Humberto
Citação
PLOS ONE, v.10, n.8, article ID e0134858, 16p, 2015
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Immune escape and metastasis are the hallmarks of several types of cancer including bladder cancer. One of the mechanisms involved in these processes has been linked to indoleamine 2,3-dioxygenase (IDO). Although IDO is classically recognized for its immunomodulatory property, it has presented nonimmunological effects in some tumors. TGF-beta 1 is believed to contribute to carcinoma development by modulating immunossupressive molecules, including IDO. In addition, TGF-beta 1 induces the epithelial-mesenchymal transition (EMT), which is a critical step in the tumor invasiveness and metastasis. We investigated the role of MT and IDO modulation in the induction of EMT by TGF-beta 1 in T24 human bladder carcinoma cells. When T24 cells were incubated with the IDO inhibitor (MT, 1-methyl-D-tryptophan), with TGF-beta 1, and with MT+TGF-beta 1, a significant decrease of IDO expression and activity was observed. In addition, downregulation of e-cadherin and upregulation of n-cadherin and EMT transcription factors were induced by the treatments, confirming the induction of EMT. siRNA-mediated knockdown of IDO decreased e-cadherin expression, but had no effect on EMT transcription factors. In the scratch-wound assay, the heightened migration process was intensified when the cells were incubated with MT+TGF-beta 1. These effects were associated with a robust inhibition of Akt activation. After inoculation of T24 cells under the kidney capsule of Balb/c nude, the cells were positive for IDO in the center of the cell infiltrate, being negative in the periphery, where EMT is high. In conclusion, inhibition of IDO by TGF-beta 1 and MT is associated with EMT in T24 human bladder carcinoma cells. MT has potentiating effect in TGF-beta 1-induced EMT, independently of IDO. This nonimmunological effect of MT should be considered if IDO is the target to avoid immune escape in bladder cancer.
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URI
https://observatorio.fm.usp.br/handle/OPI/11962
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Coleções
Artigos e Materiais de Revistas Científicas - LIM/10
Artigos e Materiais de Revistas Científicas - ODS/03