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Nicotine Enhances Colon Cancer Cell Migration by Induction of Fibronectin

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Long-term cigarette smoking increases the risk of colorectal cancer mortality. Tobacco’s addictive toxin, nicotine, was reported to increase DNA synthesis of colon cancer cells. Because metastasis is the major cause of cancer death, the influence of nicotine on the migration of colon cancer cells remains to be determined.

Methods

The influence of nicotine on the migration of colon cancer cells was evaluated using transwell assay. Nicotine receptor-mediated migration was studied by using both inhibitors and small interfering RNA (siRNA). The role of COX-2 signal was studied using pharmacological inhibitors. The expression of epithelial mesenchymal transition (EMT) marker and COX-2 signal was evaluated using real-time polymerase chain reaction (PCR).

Results

Nicotine enhanced DLD-1 and SW480 cell migration in a dose-dependent manner. We used inhibitors and siRNA to demonstrate that α7-nAChR mediates nicotine-enhanced colon cancer cell migration and upregulates fibronectin expression, which is involved in nicotine-enhanced migration. Furthermore, COX-2 signal was induced by nicotine treatment and is involved in nicotine-enhanced fibronectin expression.

Conclusions

Nicotine, tobacco’s additive toxin, enhances colon cancer metastasis through α7-nAChR and fibronectin—a mesenchymal marker for epithelial mesenchymal transition. Furthermore, COX-2 signal was involved in the induction of fibronectin. Therefore, smoking may play role in the progression of colon cancer.

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Acknowledgment

This work was supported by grant from National Science Council grant (NSC 99-2314-B-038-009-MY2), and TMU-CECR (DOH99-TD-C-111-008).

Author information

Authors and Affiliations

  1. Division of General Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan

    Po-Li Wei MD, Li-Jen Kuo MD, Weu Wang MD & Yu-Jia Chang PhD

  2. Cancer Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan

    Po-Li Wei MD & Yu-Jia Chang PhD

  3. Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Po-Li Wei MD, Li-Jen Kuo MD, Ming-Te Huang MD, Weu Wang MD & Yu-Jia Chang PhD

  4. Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan

    Ming-Te Huang MD

  5. School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan

    Yuan-Soon Ho PhD

  6. Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Yuan-Soon Ho PhD

  7. Westchester Medical Center, Hawthorne, NY, USA

    Jane An MD

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

    Li-Jen Kuo MD, Ming-Te Huang MD & Yu-Jia Chang PhD

  9. Center of Excellence for Cancer Research, Taipei Medical University, Taipei, Taiwan

    Po-Li Wei MD & Yu-Jia Chang PhD

  10. Division of Colorectal Surgery, Department of Surgery, Chung Shan Medical Hospital, Taichung, Taiwan

    Wen-Chien Ting MD

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  1. Po-Li Wei MD
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Correspondence to Yu-Jia Chang PhD.

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Li-Jen Kuo and Ming-Te Huang authors have equal contribution.

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Wei, PL., Kuo, LJ., Huang, MT. et al. Nicotine Enhances Colon Cancer Cell Migration by Induction of Fibronectin. Ann Surg Oncol 18, 1782–1790 (2011). https://doi.org/10.1245/s10434-010-1504-3

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  • DOI: https://doi.org/10.1245/s10434-010-1504-3

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