Syndecan-1, a new target molecule involved in progression of androgen-independent prostate cancer.
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 prostate cancer. Immunohistochemical analysis revealed either no or rare expression of syndecan-1 in normal secretory glands and prostate cancer cells at hormone naïve status, whereas the expression was significantly increased in viable cancer cells following neo-adjuvant hormonal therapy. Syndecan-1 expression was much higher in the androgen independent prostate cancer cell lines DU145 and PC3, rather than the androgen-dependent LNCaP, but the level in LNCaP was up-regulated in response to long-term culture under androgen deprivation. Silencing of syndecan-1 by siRNA transfection reduced endogenous production of reactive oxygen species through down-regulating NADPH oxidase 2 and induced apoptosis in DU145 and PC3 cells. Consistently, NADPH oxidase 2 knockdown induced apoptosis to a similar extent. Subcutaneous inoculation of PC3 cells in nude mice demonstrated the reduction of tumor size by localized injection of syndecan-1 siRNA in the presence of atelocollagen. Moreover, the mouse model and chorioallantoic membrane assay demonstrated significant inhibition of vascular endothelial growth factor and tumor angiogenesis by silencing of syndecan-1. In conclusion, syndecan-1 might participate in the process of androgen-dependent to -independent conversion, and be a new target molecule for hormone resistant prostate cancer therapy.
Department of Pathology, Nara Medical University School of Medicine, Shijo-cho, Kashihara, Nara, Japan.
Keiji
K
Shimada
Mitsutoshi
M
Nakamura
Marco A
MA
De Velasco
Motoyoshi
M
Tanaka
Yukiteru
Y
Ouji
Noboru
N
Konishi
D000728:Androgens / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering / Q000378:metabolism; D053668:Syndecan-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D014162:Transfection; D014183:Transplantation, Heterologous
D000728:Androgens; D034741:RNA, Small Interfering; D053668:Syndecan-1