The impact of smoking on pulmonary metastasis in colorectal cancer

Akitsugu Makino, Masashi Tsuruta, Koji Okabayashi, Takashi Ishida, Kohei Shigeta, Ryo Seishima, Akiyoshi Ikebata, Kaoru Koishikawa, Hirotoshi Hasegawa, Masayuki Shimoda, Koichi Fukunaga, Tomoko Betsuyaku, Yuko Kitagawa

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


Introduction: Recently, clinical studies have revealed that smoking can contribute to the poor prognosis of colorectal cancer (CRC) and, additionally, can be a risk factor for pulmonary metastasis of CRC. However, there has been no basic research regarding the underlying molecular mechanism. The purpose of this study was to clarify the mechanism by which smoking causes pulmonary metastasis of CRC. Methods: First, pulmonary metastasis model mice inhaled cigarette smoke or air (control) for 1 h once a day for 3 weeks. We attempted to clarify the effect of smoking on the incidence of pulmonary metastasis. On the 15th day, CMT-93 cells were injected into the tail vein. At 6 and 8 weeks following injection, the extent of pulmonary metastasis was evaluated using in vivo micro CT. After the last CT examination, the mice were sacrificed, and the lungs were extracted for pathological examination. Results: The number of mice with pulmonary metastases in the smoking group was significantly higher than in the control group. Three weeks of smoking induced mild inflammation in the lungs, as evidenced by increases in the levels of IL-6 and TNF-α in bronchoalveolar lavage. Moreover, the adhesion-related molecule ICAM-1 was overex-pressed in pulmonary tissue, which allowed drained cancer cells to remain in the lung and contribute to the formation of pulmonary metastasis. Conclusion: Collectively, cigarette smoking may contribute to the pathogenesis and development of pulmonary metastasis in CRC through enhancement of adhesion and inflammation.

Original languageEnglish
Pages (from-to)9623-9629
Number of pages7
JournalOncoTargets and Therapy
Publication statusPublished - 2020


  • Adhesion molecules
  • Colorectal cancer
  • ICAM-1
  • Pulmonary metastasis
  • Smoking

ASJC Scopus subject areas

  • Oncology
  • Pharmacology (medical)


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