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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 10
Affiliation:
[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
Total Affiliations: 3
Document type: Journal article
Source: PLoS One; v. 10, n. 8 AUG 12 2015.
Web of Science Citations: 6
Abstract

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)

FAPESP's process: 12/04423-0 - Role of indoleamine 2,3 dioxygenase (IDO) in the process of epithelial-mesenchymal transition(EMT) mediated by TGF-beta in human urogenital carcinoma
Grantee:Humberto Dellê
Support Opportunities: Regular Research Grants