The Impact of Smoking on Pulmonary Metastasis in Colorectal Cancer.

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 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.
Competing Interests: Prof. Dr. Yuko Kitagawa reports grants and/or personal fees from ASAHI KASEI PHARMA CO., LTD., TAIHO PHARMACEUTICAL CO., LTD, CHUGAI PHARMACEUTICAL CO., LTD., DAIICHI SANKYO COMPANY, LIMITED, Merck Serono Co., Ltd., EA Pharma Co., Ltd., Yakult Honsha Co. Ltd., Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Factory Inc., SHIONOGI & CO., LTD., KAKEN PHARMACEUTICAL CO., LTD., Kowa Pharmaceutical Co., Ltd., Astellas Pharma Inc., MEDICON INC., DAINIPPON SUMITOMO PHARMA Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Pfizer Japan Inc., ONO PHARMACEUTICAL CO., LTD., NIHON PHARMACEUTICAL CO., LTD., Japan Blood Products Organization, Medtronic Japan Co., Ltd., Sanofi K.K., Eisai Co., Ltd., TSUMURA & CO., KCI Licensing, Inc., ABBOTT JAPAN CO., LTD., FUJIFILM Toyama Chemical Co., Ltd., outside the submitted work. The authors report no other conflicts of interest in this work.
(© 2020 Makino et al.)