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Syndecan‐1 ( CD138 ) contributes to prostate cancer progression by stabilizing tumour‐initiating cells
Author(s) -
Shimada Keiji,
Anai Satoshi,
Fujii Tomomi,
Tanaka Nobumichi,
Fujimoto Kiyohide,
Konishi Noboru
Publication year - 2013
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4271
Subject(s) - prostate cancer , tramp , cancer research , cd44 , cancer cell , docetaxel , cancer stem cell , cancer , gene silencing , tumor progression , syndecan 1 , adenocarcinoma , biology , chemistry , medicine , cell , biochemistry , gene
Increasing evidence suggests that tumour‐initiating cells ( TICs ) contribute to the development of prostate cancer. Here, we identified syndecan‐1 as a key molecule maintaining the stability of prostate cancer TICs . Holoclones harbouring the biological properties of stemness were derived from single‐cell cultures of the PC3 human prostate cancer cell line. These holoclones over‐expressed syndecan‐1, but showed reduced expression of NADPH oxidase ( NOX ) and synthesis of hydrogen peroxide and oxygen radicals. Stable RNA ‐mediated silencing of syndecan‐1 gene expression up‐regulated NOX ‐dependent generation of reactive oxygen species and reduced the survival of holoclones in vitro . Syndecan‐1 down‐regulation also strongly reduced the number of CD133 + / CD44 + primitive cancer cells and tumour growth in vivo . Interestingly, syndecan‐1 gene knockdown significantly enhanced the tumour‐suppressive effects of docetaxel by inhibiting the docetaxel‐induced increase in CD133 + / CD44 + cells in vivo . In the transgenic adenocarcinoma of the mouse prostate ( TRAMP ) mouse model of prostate cancer, early intervention with a syndecan‐1 inhibitor ( OGT2115 ) or syndecan‐1 RNAi reduced the incidence of adenocarcinoma and the number of c‐kit + / CD44 + cells in cancer foci. Finally, we found that syndecan‐1 immunopositivity in prostate cancer cells was significantly associated with biochemical recurrence after radical prostatectomy. Taken together, our results show that syndecan‐1 contributes to prostatic carcinogenesis by maintaining TICs and may be a target molecule for therapy. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.