Role of syndecan-1 (CD138) in cell survival of human urothelial carcinoma.

Abstract

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.

• Authors: Keiji Shimada, Mitsutoshi Nakamura, Marco A De Velasco, Motoyoshi Tanaka, Yukiteru Ouji, Makito Miyake, Kiyohide Fujimoto, Kazuya Hirao, Noboru Konishi
• Journal: Cancer science (Cancer Sci) Vol. 101 Issue 1 Pg. 155-60 (Jan 2010) ISSN: 1349-7006 [Electronic] England
• PMID: 19860843 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Small Interfering
• SDC1 protein, human
• Syndecan-1

Topics

• Adult
• Aged
• Aged, 80 and over
• Animals
• Apoptosis
• Cell Line, Tumor
• Cell Survival
• Female
• Humans
• Male
• Mice
• Middle Aged
• RNA, Small Interfering (genetics)
• Syndecan-1 (analysis, antagonists & inhibitors, physiology)
• Urinary Bladder Neoplasms (pathology)