Santos Hellen Joyce Sousa Pereira, Matheus Luiz Henrique Gomes, Silva Aline, Dalmazzo Stephanie Vanin, Santos Andressa Assunção, Santos Letícia Rafaela Alves Rubens, Souza Diego Mota, Reis Sabrina Thalita, Nascimento Ivan Pereira, Dellê Humberto
Postgraduate Program in Medicine, Universidade Nove de Julho (UNINOVE), São Paulo, Brazil.
Laboratory of Medical Investigation (LIM55), Urology Department, University of São Paulo Medical School, Sao Paulo, Brazil.
Int J Tryptophan Res. 2022 Jan 4;15:11786469211065612. doi: 10.1177/11786469211065612. eCollection 2022.
The severity of the bladder carcinoma (BC) is directly linked to cell invasion and metastasis. Indoleamine 2,3-dioxygenase-1 (IDO-1) is an INF-γ-induced immunomodulating enzyme that has been linked to the cancer cell invasiveness. Because IDO1 is variable among the tumors, we analyzed its expression in the BC invasion using BC mice models and cell culture. MB49 cells were orthotopically or ectopically inoculated in C57Bl6 mice to evaluate IDO1 by immunohistochemistry. For in vitro experiments, expression of IDO1 and INF-γ was evaluated in grade-1 (RT4) and in grade-3 (T24) BC cell lines. Invading and non-invading T24 cells were separated using the Matrigel/Transwell system, of which total RNA was extracted immediately or after 2 weeks of subculture. Finally, IDO1 was silenced in T24 cells to verify its role on cell invasiveness. In both animal models, IDO1 was differentially expressed between non-invading and invading cells. In cell culture, T24 cells expressed more IDO1 than RT4 cells, independently of the INF-γ expression. IDO1 was differentially expressed between non-invading and invading T24 cells, a difference that was lost by long-time subculture. IDO1 silencing resulted in diminished cell invasiveness. In conclusion, IDO1 expression is changed during bladder carcinoma invasion, playing an important role in this process.
膀胱癌（BC）的严重程度与细胞侵袭和转移直接相关。吲哚胺2,3-双加氧酶-1（IDO-1）是一种由INF-γ诱导的免疫调节酶，与癌细胞的侵袭性有关。由于IDO1在肿瘤之间存在差异，我们使用BC小鼠模型和细胞培养分析了其在BC侵袭中的表达。将MB49细胞原位或异位接种到C57Bl6小鼠中，通过免疫组织化学评估IDO1。对于体外实验，在1级（RT4）和3级（T24）BC细胞系中评估IDO1和INF-γ的表达。使用基质胶/Transwell系统分离侵袭性和非侵袭性T24细胞，立即或在传代培养2周后提取其总RNA。最后，在T24细胞中沉默IDO1以验证其对细胞侵袭性的作用。在两种动物模型中，IDO1在非侵袭性和侵袭性细胞之间差异表达。在细胞培养中，T24细胞比RT4细胞表达更多的IDO1，与INF-γ表达无关。IDO1在非侵袭性和侵袭性T24细胞之间差异表达，这种差异在长期传代培养后消失。IDO1沉默导致细胞侵袭性降低。总之，IDO1表达在膀胱癌侵袭过程中发生变化，在此过程中起重要作用。
