| Texto completo | |
| Autor(es): |
Oliveira Brito, Rodrigo Barbosa
[1]
;
Malta, Camila Soares
[1]
;
Souza, Diego Mota
[1]
;
Gomes Matheus, Luiz Henrique
[1]
;
Teles Matos, Yves Silva
[1]
;
Silva, Chrisna Souza
[1]
;
Ferreira, Janaina Mendes
[1]
;
Nunes, Valeria Sutti
[2]
;
Franca, Cristiane Miranda
[3]
;
Delle, Humberto
[1]
Número total de Autores: 10
|
| Afiliação do(s) autor(es): | [1] Univ Nove Julho Uninove, Programa Posgrad Med, Sao Paulo - Brazil
[2] Univ Sao Paulo, Fac Med Sci, Endocrinol & Metab Div Hosp Clin, Lipids Lab LIM 10, Sao Paulo - Brazil
[3] Univ Nove Julho UNINOVE, Programa Posgrad Biofoton Ciencias Saude, Sao Paulo - Brazil
Número total de Afiliações: 3
|
| Tipo de documento: | Artigo Científico |
| Fonte: | PLoS One; v. 10, n. 8 AUG 12 2015. |
| Citações Web of Science: | 6 |
| 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. (AU) | |
| Processo FAPESP: | 12/04423-0 - Papel da enzima indoleamina 2,3 dioxigenase (IDO) no processo de transição epitélio-mesenquimal (EMT) mediada por TGF-beta em carcinoma urogenital humano |
| Beneficiário: | Humberto Dellê |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |