Open AccessRole of syndecan‐1 (CD138) in cell survival of human urothelial carcinoma
Author(s) -
Shimada Keiji,
Nakamura Mitsutoshi,
De Velasco Marco A.,
Tanaka Motoyoshi,
Ouji Yukiteru,
Miyake Makito,
Fujimoto Kiyohide,
Hirao Kazuya,
Konishi Noboru
Publication year - 2010
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01379.x
Subject(s) - syndecan 1 , cancer research , junb , gene silencing , apoptosis , bladder cancer , gene knockdown , cancer , urothelial cell , transfection , cancer cell , medicine , cell , pathology , biology , cell culture , gene expression , gene , biochemistry , genetics
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 ≥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. ( Cancer Sci 2009)