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Thrombomodulin mediates the migratory ability of hormone-independent prostate cancer cells through the regulation of epithelial-to-mesenchymal transition biomarkers

  • Research Article
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Tumor Biology

Abstract

Thrombomodulin (TM) is highly expressed in endothelial cells and plays the key role in maintaining physical homeostasis. In addition, many pieces of evidence also show that TM contains the diagnostic value for malignant diseases. TM has been found to correlate with metastatic status in multiple cancers, but its role in prostate cancer progression remains unclear. TM expression was determined in prostate cancer cells (DU-145 and PC-3 cells) using real-time PCR and Western blotting. TM expression was manipulated in prostate cancer cells using TM-specific shRNA and an overexpression system. The proliferation, adhesion, and migratory ability of prostate cancer cells expressing various TM levels were determined using the x’Celligence biosensor system and a transwell migration assay. Higher levels of TM transcription and translation were found in DU-145 cells and were negatively correlated with the low migratory ability of DU-145 cells. After silencing TM expression in DU-145 cells, cell growth decreased, but cell adhesion and migration dramatically increased. TM overexpression in PC-3 cells reduced their metastatic ability. We investigated the possible mechanisms of this phenomenon and determined that the enhanced cell migration was mediated through the expression of E-cadherin and vimentin. TM may be a modulator of hormone-independent prostate cancer (HIPC) metastasis. The downregulation of TM expression enhanced the migratory ability of these cells via an increase in vimentin expression and a decrease in E-cadherin expression.

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Acknowledgments

This study was supported by a grant from Chang Gung Memorial Hospital (CMRPG2B0323) and a grant from Taipei Medical University (TMU100-AE3-Y14).

Conflicts of interest

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Authors and Affiliations

  1. Department of Urology, Chang Gung Memorial Hospital, Keelung, Taiwan

    Chun-Te Wu

  2. Chang Gung University College of Medicine and Chang Gung Institute of Technology, Tao-Yuan, Taiwan

    Chun-Te Wu & Miao-Fen Chen

  3. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Yu-Jia Chang & Po-Li Wei

  4. Department of Surgery, Taipei Medical University, Taipei, Taiwan

    Yu-Jia Chang, Po-Li Wei & Weu Wang

  5. Division of General Surgery, Taipei Medical University and Hospital, Taipei, Taiwan

    Yu-Jia Chang, Po-Li Wei & Weu Wang

  6. Cancer Research Center, Taipei Medical University and Hospital, Taipei, Taiwan

    Yu-Jia Chang & Po-Li Wei

  7. Department of Radiation Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan

    Miao-Fen Chen

  8. School of Medical Laboratory Science and Biotechnology, Taipei Medical University, Taipei, Taiwan

    Jun-Jen Liu

  9. Department of Public Health, School of Public Health, Taipei Medical University, 250 Wu-Xin Street, Taipei City, 110, Taiwan

    Hui-Hsiung Liu

Authors
  1. Chun-Te Wu
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  2. Yu-Jia Chang
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  3. Miao-Fen Chen
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  4. Jun-Jen Liu
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  5. Po-Li Wei
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  6. Weu Wang
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  7. Hui-Hsiung Liu
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Corresponding authors

Correspondence to Weu Wang or Hui-Hsiung Liu.

Additional information

Chun-Te Wu and Yu-Jia Chang contributed equally to this work.

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Wu, CT., Chang, YJ., Chen, MF. et al. Thrombomodulin mediates the migratory ability of hormone-independent prostate cancer cells through the regulation of epithelial-to-mesenchymal transition biomarkers. Tumor Biol. 35, 6047–6054 (2014). https://doi.org/10.1007/s13277-014-1801-8

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  • DOI: https://doi.org/10.1007/s13277-014-1801-8

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