High expression of Notch ligand Jagged2 is associated with the metastasis and recurrence in urothelial carcinoma of bladder.
BACKGROUND
The Notch signaling pathway is closely related with human organ development and tumorgenisis. Jagged2 is among the most popular topic in Notch studies currently. Recent studies found its vital role in tumor metastasis in breast cancer; however, its expression profile and its prognostic value in urothelial carcinoma of bladder have not been investigated.


METHODS
Immunohistochemistry was used to detect the expression of Jagged2 in 120 bladder urothelial carcinoma. Moreover, the expression of Jagged2 was analyzed by Western blot in 60 bladder urothelial carcinoma and 20 normal epithelial tissues. MTT assay and flow cytometry and transwell assay were used to examine the proliferative and invasive ability of bladder cancer cells with the treatment of GSIXX (the inhibitor of Jagged2). Prognostic value of Jagged2 expression and its correlation with tumor metastasis and recurrence were evaluated, and the proliferative and invasive ability and cell cycle process of the bladder cancer cells were detected as well.


RESULTS
There was a significantly higher Jagged2 expressions in bladder urothelial carcinoma and highly invasive bladder T24 cells than those in bladder normal tissues and the superficial bladder BIU-87 cells. Jagged2 expression was positively correlated with histological grade, p T stage, recurrence, and metastasis. With the increasing concentration of GSIXX, we found that not only the cell proliferation and invasion activity decreased significantly, but also the cell cycle was blocked at G2/M stage.


CONCLUSIONS
Jagged2 expression status was closely correlated with important histopathologic characteristics (grades and stages) and the recurrence and metastasis of bladder urothelial carcinomas. Furthermore, Jagged2 played an important function on the bladder cancer cells' proliferation by regulating the cancer cell cycle from G1/S to G2/M and probably promoted the invasion and metastasis of bladder cancer.
Department of Urology, Shanghai Tenth People's Hospital, Tongji University Shanghai, 200072, China.
Wei
W
Li
Min
M
Liu
Yuan
Y
Feng
Yan-Fei
YF
Huang
Yun-Fei
YF
Xu
Jian-Ping
JP
Che
Guang-Chun
GC
Wang
Jun-Hua
JH
Zheng
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D002277:Carcinoma / Q000378:metabolism* / Q000556:secondary / Q000601:surgery; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003984:Dibenzazepines / Q000494:pharmacology; D018572:Disease-Free Survival; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D000072101:Jagged-2 Protein; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D013997:Time Factors; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D019459:Urothelium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; D003984:Dibenzazepines; D036341:Intercellular Signaling Peptides and Proteins; C490504:JAG2 protein, human; D000072101:Jagged-2 Protein; D008565:Membrane Proteins; C527817:dibenzazepine
Bladder urothelial carcinoma; GSIXX; Jagged2; clinical stage; histopathologic grade