Details

Autor(en) / Beteiligte

• Shimada, Keiji
• Nakamura, Mitsutoshi
• De Velasco, Marco A.
• Tanaka, Motoyoshi
• Ouji, Yukiteru
• Konishi, Noboru

Titel

Syndecan‐1, a new target molecule involved in progression of androgen‐independent prostate cancer

Ist Teil von

• Cancer science, 2009-07, Vol.100 (7), p.1248-1254

Ort / Verlag

Melbourne, Australia: Blackwell Publishing Asia

Erscheinungsjahr

2009

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. (Cancer Sci 2009; 100: 1248–1254)