Relationship between cysteinyl-leukotriene-1 receptor and human transitional cell carcinoma in bladder.
OBJECTIVE
To investigate the leukotriene (LT) D(4) (LTD(4)) receptor (cysteinyl-LT(1) receptor [CysLT(1)R]) expression in transitional cell carcinoma (TCC) of the bladder, as well as the effects of the CysLT(1)R antagonist on cell proliferation in TCC cell lines. The metabolism of arachidonic acid by either cyclooxygenase or lipoxygenase is thought to play an important role in carcinogenesis. LTD(4) is a pro-inflammatory mediator derived from arachidonic acid through various enzymatic steps, and 5-lipoxygenase is an important factor in generating LTD(4).


METHODS
CysLT(1)R expression in TCC tissue and normal bladder tissue was examined. CysLT(1)R expression was detected using immunohistochemistry. The effects of the CysLT(1)R antagonist on TCC cell growth were examined by 3-(4,5-dimethylthiazol-2-thiazolyl)-2,5-diphenyltetrazolium bromide assay and reverse transcriptase-polymerase chain reaction. Flow cytometry was used to determine whether the CysLT(1)R antagonist induced apoptosis.


RESULTS
Initially, only slight CysLT(1)R expression was detected in normal bladder tissues and marked CysLT(1)R expression was detected in the TCC tissues. CysLT(1)R expression was greater in high-grade cancer than in low-grade cancer. Furthermore, CysLT(1)R expression was also greater in advanced-stage cancer than in early-stage cancer. Finally, the CysLT(1)R antagonist caused marked inhibition of TCC cells by inducing early apoptosis.


CONCLUSIONS
CysLT(1)R was induced in TCC. The results suggest that the CysLT(1)R antagonist might mediate potent antiproliferative effects on TCC cells. Thus, the target of the CysLT(1)R is potentially a new therapy in the treatment of TCC.
Matsuyama
Masahide
M
Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Funao
Kiyoaki
K
Hayama
Takuma
T
Tanaka
Tomoaki
T
Kawahito
Yutaka
Y
Sano
Hajime
H
Takemoto
Yoshiaki
Y
Nakatani
Tatsuya
T
Yoshimura
Rikio
R
D002295:Carcinoma, Transitional Cell / Q000378:metabolism*; D006801:Humans; D018077:Receptors, Leukotriene / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
D018077:Receptors, Leukotriene; C083169:leukotriene D4 receptor