title: Suppressing tumourigenicity of prostate cancer cells by inhibiting osteopontin expression.
abstract: Expression of osteopontin (OPN) is increased in prostate cancer cells. The possibility of utilising the increased OPN as a target to suppress the tumourigenicity was investigated in this study. Small interference RNAs against OPN were transfected into highly malignant DU145 prostate cancer cells, which express high level of OPN prior to the transfections, to establish OPN-suppressed clones. Compared with the control transfectants generated by scrambled RNA, suppressed expression of OPN significantly inhibited cell invasiveness and anchorage-independent growth. Similar results were obtained from in vivo experiments. OPN-suppressed transfectants produced significant reductions in average sizes of subcutaneous tumours after inoculation into nude mice. When the levels of OPN measured in transfectants before injection were related to tumour sizes, the reduction in tumour sizes was not propotionally related to the inhibition in OPN-levels. However, when the levels of OPN were analysed in the tumour tissues, it was found that the reduced OPN expression levels were significantly associated with the reducing tumour sizes. These results showed that changes in OPN levels had occurred after the transfectants were inoculated in mice. This study suggested while OPN can be an effective target for therapeutic suppression of prostate cancer, more effective way than RNAi is needed to inhibit OPN expression.
authors.affiliation: Molecular Pathology Laboratory, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, 6th Floor, Duncan Building, Daulby Street, Liverpool L69 3GA, UK.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shiva S
authors.initials: SS
authors.lastname: Forootan
authors.forename: Laleh
authors.initials: L
authors.lastname: Kamalian
authors.forename: Zheng Z
authors.initials: ZZ
authors.lastname: Bao
authors.forename: Mohammed I
authors.initials: MI
authors.lastname: Malki
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Foster
authors.forename: Youqiang
authors.initials: Y
authors.lastname: Ke
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D053495:Osteopontin / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D034741:RNA, Small Interfering; D053495:Osteopontin