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Author Notes:

Correspondence: Chia-Ling Hsieh, email: chsieh2@tmu.edu.tw

We thank Dr. Mien-Chie Hung at M.D. Anderson Cancer Center for providing us with the SN liposome and Dr. Robert H. Lyles at Emory University for statistical analysis.

The authors have no conflicts of interest to declare.

Subjects:

Research Funding:

his work was supported in part by grant W81XWH-05-1-0024 from the Department of Defense in USA, and grant NSC102-2320-B-039-058, 96-2628-B-039-029-MY3 from the National Science Council, MOHW103-TD-B-111-01 from the Ministry of Health and Welfare, and TMU 102-AE1-B16, 102-AE1-B01 from Taipei Medical University in Taiwan.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • Cell Biology
  • L1 cell adhesion molecule (L1CAM)
  • prostate cancer
  • bone metastasis
  • gene therapy
  • small interfering RNA (siRNA)
  • RNA INTERFERENCE
  • TUMOR PROGRESSION
  • OVARIAN-CANCER
  • MATRIX METALLOPROTEINASE-2
  • CARCINOMA-CELLS
  • GASTRIC-CANCER
  • SOLUBLE FORM
  • L1CAM
  • MIGRATION
  • INVOLVEMENT

Targeting L1 cell adhesion molecule expression using liposome-encapsulated siRNA suppresses prostate cancer bone metastasis and growth

Tools:

Journal Title:

Oncotarget

Volume:

Volume 5, Number 20

Publisher:

, Pages 9911-9929

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2014 Sung et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/).

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