OncoTargets and Therapy (Sep 2020)

The Impact of Smoking on Pulmonary Metastasis in Colorectal Cancer

  • Makino A,
  • Tsuruta M,
  • Okabayashi K,
  • Ishida T,
  • Shigeta K,
  • Seishima R,
  • Ikebata A,
  • Koishikawa K,
  • Hasegawa H,
  • Shimoda M,
  • Fukunaga K,
  • Betsuyaku T,
  • Kitagawa Y

Journal volume & issue
Vol. Volume 13
pp. 9623 – 9629

Abstract

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Akitsugu Makino,1 Masashi Tsuruta,1 Koji Okabayashi,1 Takashi Ishida,1 Kohei Shigeta,1 Ryo Seishima,1 Akiyoshi Ikebata,1 Kaoru Koishikawa,1 Hirotoshi Hasegawa,2 Masayuki Shimoda,3 Koichi Fukunaga,4 Tomoko Betsuyaku4 ,* Yuko Kitagawa1 1Department of Surgery, Keio University School of Medicine, Tokyo, Japan; 2Department of Surgery, Tokyo Dental College Ichikawa General Hospital, Chiba, Japan; 3Department of Pathology, Keio University School of Medicine, Tokyo, Japan; 4Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan†Professor Tomoko Betsuyaku passed away on September 1, 2018.Correspondence: Masashi Tsuruta Department of SurgeryKeio University School of Medicine, 35 Shinanomachi Shinjyuku-Ku, Tokyo 160-8582, JapanTel +81-3-3353-1211Fax +81-3-3355-4707Email [email protected]: 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 overexpressed 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.Keywords: smoking, colorectal cancer, pulmonary metastasis, adhesion molecules, ICAM-1

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