Oncotarget

Research Papers:

Targeting L1 cell adhesion molecule expression using liposome-encapsulated 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 and Chia-Ling Hsieh _

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Oncotarget. 2014; 5:9911-9929. https://doi.org/10.18632/oncotarget.2478

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Abstract

Shian-Ying Sung1,2, I-Hui Wu2,*, Pei-Hsin Chuang2,*, John A. Petros3,5, Hsi-Chin Wu4, Hong-Jie Zeng1, Wei-Chien Huang2, Leland W. K. Chung3,6 and Chia-Ling Hsieh1,2,3,7

1 The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan

2 Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan

3 Department of Urology, Emory University, Atlanta, GA, USA

4 School of Medicine, China Medical University, Taichung, Taiwan

5 Department of Urology, Atlanta VA Medical Center, Decatur GA, USA

6 Department of Medicine, Cedars Sinai Medical Center, Los Angeles, CA, USA

7 Department of Biotechnology, Asia University, Wufeng, Taichung,  aiwan

* These authors contributed equally to this work

Correspondence:

Chia-Ling Hsieh, email:

Keywords: L1 cell adhesion molecule (L1CAM), prostate cancer, bone metastasis, gene therapy, small interfering RNA (siRNA)

Received: July 02, 2014 Accepted: September 15, 2014 Published: September 16, 2014

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 liposome-encapsulated 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.


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