Integrin β4 and vinculin contained in exosomes are potential markers for progression of prostate cancer associated with taxane-resistance

Kyojiro Kawakami, Yasunori Fujita, Taku Kato, Kosuke Mizutani, Koji Kameyama, Hiroki Tsumoto, Yuri Miura, Takashi Deguchi, Masafumi Ito

研究成果: Article査読

69 被引用数 (Scopus)

抄録

Treatment with taxanes for castration-resistant prostate cancer often leads to the development of resistance. It has been recently demonstrated that exosomes present in the body fluids contain proteins and RNAs in the cells from which they are derived and could serve as a diagnostic marker for various diseases. In the present study, we aimed to identify proteins contained in exosomes that could be markers for progression and taxane-resistance of prostate cancer. Exosomes were isolated by differential centrifugation from the culture medium of taxane-resistant human prostate cancer PC-3 cells (PC-3R) and their parental PC-3 cells. Isolated exosomes were subjected to iTRAQ-based quantitative proteomic analysis. Exosomes were also isolated from the culture medium by using anti-CD9 antibody-conjugated magnetic beads. Protein expression was knocked down by siRNA transfection followed by analysis of the silencing effects. Proteomic analysis showed that integrin β4 (ITGB4) and vinculin (VCL) were upregulated in exosomes derived from PC-3R cells compared to PC-3 cells. The elevation of ITGB4 and VCL was confirmed in exosomes captured by anti-CD9 antibody from the culture medium of PC-3R cells. Silencing of ITGB4 and VCL expression did not affect proliferation and taxane-resistance of PC-3R cells, but ITGB4 knockdown attenuated both cell migration and invasion and VCL knockdown reduced invasion. Our results suggest that ITGB4 and VCL in exosomes could be useful markers for progression of prostate cancer associated with taxane-resistance, providing the basis for development of an exosome-based diagnostic system.

本文言語English
ページ(範囲)384-390
ページ数7
ジャーナルInternational journal of oncology
47
1
DOI
出版ステータスPublished - 01-07-2015
外部発表はい

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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