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https://observatorio.fm.usp.br/handle/OPI/11962
Title: | 1-Methyl-D-Tryptophan Potentiates TGF-beta-Induced Epithelial-Mesenchymal Transition in T24 Human Bladder Cancer Cells |
Authors: | BRITO, Rodrigo Barbosa Oliveira; MALTA, Camila Soares; SOUZA, Diego Mota; MATHEUS, Luiz Henrique Gomes; MATOS, Yves Silva Teles; SILVA, Chrisna Souza; FERREIRA, Janaina Mendes; NUNES, Valeria Sutti; FRANCA, Cristiane Miranda; DELLE, Humberto |
Citation: | PLOS ONE, v.10, n.8, article ID e0134858, 16p, 2015 |
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. |
Appears in Collections: | Artigos e Materiais de Revistas Científicas - LIM/10 Artigos e Materiais de Revistas Científicas - ODS/03 |
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art_BRITO_1MethylDTryptophan_Potentiates_TGFbetaInduced_EpithelialMesenchymal_Transition_in_T24_Human_2015.PDF | publishedVersion (English) | 8.75 MB | Adobe PDF | View/Open |
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