| First Author | Shimada K | Year | 2013 |
| Journal | J Pathol | Volume | 231 |
| Issue | 4 | Pages | 495-504 |
| PubMed ID | 24549646 | Mgi Jnum | J:206809 |
| Mgi Id | MGI:5553001 | Doi | 10.1002/path.4271 |
| Citation | Shimada K, et al. (2013) Syndecan-1 (CD138) contributes to prostate cancer progression by stabilizing tumour-initiating cells. J Pathol 231(4):495-504 |
| abstractText | 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 (c) 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
