Targeting ECM-integrin interaction with liposome-encapsulated small interfering RNAs inhibits the growth of human prostate cancer in a bone xenograft imaging model

Kristen Bisanz, Jie Yu, Magnus Edlund, Bill Spohn, Mien Chie Hung, Leland W.K. Chung, Chia Ling Hsieh

研究成果: 雜誌貢獻文章同行評審

74 引文 斯高帕斯(Scopus)

摘要

The intricate intracellular communication between stromal and epithelial cells, which involves cell-cell-, cell-insoluble extracellular matrix- (ECM), and cell-soluble factor-mediated signaling processes, is an attractive target for therapeutic intervention in hormone-refractory and bone-metastatic prostate cancer. In the present study we demonstrated that androgen-independent PC3 prostate cancer cells adhered to and migrated on vitronectin (VN), a major noncollagenous ECM in mature bone, through the expression of αv-containing integrin receptors αvβ1 and αvβ5 on the cell surface, as determined by antibody function blocking assay and flow cytometry analysis. Small interfering RNAs (siRNAs) targeting human integrin αv markedly reduced their respective mRNA and protein expression in cells, resulting in nearly complete reduction in VN-mediated cancer progression in vitro. In vivo quantitative bioluminescence analysis of human prostate cancer bone xenografts demonstrated for the first time that intratumoral administration of liposome-encapsulated human αv-siRNAs significantly inhibits the growth of luciferase-tagged PC3 tumors in skeleton, which was associated with decreased integrin αv expression and increased apoptosis in tumor cells. This integrin-based gene therapy is particularly suitable for the treatment of prostate cancer bone metastasis.
原文英語
頁(從 - 到)634-643
頁數10
期刊Molecular Therapy
12
發行號4
DOIs
出版狀態已發佈 - 10月 2005
對外發佈

ASJC Scopus subject areas

  • 分子醫學
  • 分子生物學
  • 遺傳學
  • 藥理
  • 藥物發現

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