Role of syndecan-1 (CD138) in cell survival of human urothelial carcinoma.
Heparan sulfate proteoglycan syndecan-1, CD138, is well known to be associated with cell proliferation, adhesion, and migration in various types of malignancies. In the present study, we focused on the role of syndecan-1 in human urothelial carcinoma of the urinary bladder. Silencing of syndecan-1 by siRNA transfection down-regulated transcriptional factor junB and the long isoform of FLICE-inhibitory protein (FLIP long), resulting in the induction of apoptosis in the urothelial carcinoma cell lines UMUC2 and UMUC3. Knockdown of junB and FLIP long as well as syndecan-1 silencing mediated apoptosis that was inhibited by pan-caspase inhibitors. Transurethral injection of syndecan-1 siRNA into the urinary bladder significantly reduced syndecan-1 gene expression and growth of red fluorescent-labeled KU-7/RFP bladder cancer cells in the mouse orthotopic bladder cancer model. Immunohistochemical examination showed high syndecan-1 protein expression in high-grade, superficial, and deep invasive carcinomas (pT1 and >or=pT2) as well as carcinoma in situ, but not in low-grade and noninvasive phenotypes (pTa). In addition, the percentage of cancer cells positive for syndecan-1 at initial diagnosis was statistically associated with the frequency of bladder cancer recurrence after transurethral resection. In conclusion, syndecan-1 might contribute to urothelial carcinoma cell survival and progression; therefore, this molecule could be a new therapeutic target in human urinary bladder cancer.
Department of Pathology, Nara Medical University School of Medicine, Nara, Japan.
Keiji
K
Shimada
Mitsutoshi
M
Nakamura
Marco A
MA
De Velasco
Motoyoshi
M
Tanaka
Yukiteru
Y
Ouji
Makito
M
Miyake
Kiyohide
K
Fujimoto
Kazuya
K
Hirao
Noboru
N
Konishi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D034741:RNA, Small Interfering / Q000235:genetics; D053668:Syndecan-1 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
D034741:RNA, Small Interfering; C508241:SDC1 protein, human; D053668:Syndecan-1