Targeting L1 cell adhesion molecule expression using liposomeencapsulated siRNA suppresses prostate cancer bone metastasis and growth

Shian Ying Sung, I. Hui Wu, Pei Hsin Chuang, John A. Petros, Hsi Chin Wu, Hong Jie Zeng, Wei Chien Huang, Leland W K Chung, Chia Ling Hsieh

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13 Citations (Scopus)

Abstract

The L1 cell adhesion molecule (L1CAM) has been implicated in tumor progression of many types of cancers, but its role in prostate cancer and its application in targeted gene therapy have not been investigated. Herein, we demonstrated that the L1CAM was expressed in androgen-insensitive and highly metastatic human prostate cancer cell lines. The correlation between L1CAM expression and prostate cancer metastasis was also validated in serum samples of prostate cancer patients. Knockdown of L1CAM expression in prostate cancer cells by RNA interference significantly decreased their aggressive behaviors, including colony formation, migration and invasion in vitro, and tumor formation in a metastatic murine model. These anti-malignant phenotypes of L1CAM-knockdown cancer cells were accompanied by G0/G1 cell cycle arrest and suppression of matrix metalloproteinase (MMP)-2 and MMP-9 expression and nuclear factor NF-κB activation. In vivo targeting of L1CAM expression using liposomeencapsulated L1CAM siRNAs effectively inhibited prostate cancer growth in mouse bone, which was associated with decreased L1CAM expression and cell proliferation by tumor cells. These results provide the first evidence for L1CAM being a major contributor to prostate cancer metastasis and translational application of siRNA-based L1CAM-targeted therapy.

Original languageEnglish
Pages (from-to)9911-9929
Number of pages19
JournalOncotarget
Volume5
Issue number20
Publication statusPublished - 2014

Keywords

  • Bone metastasis
  • Gene therapy
  • L1 cell adhesion molecule (L1CAM)
  • Prostate cancer
  • Small interfering RNA (siRNA)

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Sung, S. Y., Wu, I. H., Chuang, P. H., Petros, J. A., Wu, H. C., Zeng, H. J., Huang, W. C., Chung, L. W. K., & Hsieh, C. L. (2014). Targeting L1 cell adhesion molecule expression using liposomeencapsulated siRNA suppresses prostate cancer bone metastasis and growth. Oncotarget, 5(20), 9911-9929.