RT Journal Article SR Electronic T1 A Potential Role of Adhesion Molecules on Lung Metastasis Enhanced by Local Inflammation JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 6171 OP 6178 DO 10.21873/anticanres.14637 VO 40 IS 11 A1 HIROYUKI HORIGUCHI A1 HIRONORI TSUJIMOTO A1 NARIYOSHI SHINOMIYA A1 YUSUKE MATSUMOTO A1 HIDEKAZU SUGASAWA A1 TAKAO YAMORI A1 HIROMI MIYAZAKI A1 DAIZOH SAITOH A1 YOJI KISHI A1 HIDEKI UENO YR 2020 UL http://ar.iiarjournals.org/content/40/11/6171.abstract AB Background/Aim: Local and systemic inflammations are associated with negative long-term outcomes; however, their precise mechanism of action remains unclear. We previously demonstrated that hepatocyte growth factor (HGF)/c-Met signaling contributed to the enhancement of liver metastasis associated with peritonitis model. The aim of this study is to investigate the effect of local inflammation on the development of lung metastasis. Materials and Methods: NL-17 cells were injected into BALB/c mice via the tail vein to produce a high potential model for lung metastasis. After injection of NL-17 cells, lipopolysaccharide (LPS) and live Pseudomonas aeruginosa, and phosphate-buffered saline were administered intratracheally to induce acute lung injury (ALI) and pneumonia, respectively. Results: In both ALI and pneumonia mice, lung metastasis was significantly promoted compared to control mice. Concentrations of Interleukin-6, tumor necrosis factor-α, and HGF in the bronchoalveolar lavage fluid were significantly higher in ALI and pneumonia mice than in control mice. Neither administration of recombinant mouse HGF nor c-Met knockdown in NL-17 cells influenced the magnitude of lung metastasis. Yet stimulation with LPS increased the expression of α2 integrin, vascular cell-adhesion protein-1, and intercellular adhesion molecule-1 (ICAM-1) in the lung. Invasive activity of NL-17 cells was significantly up-regulated by LPS, but was suppressed by anti-ICAM-1 antibody. While LPS-stimulated NL-17 cells showed significantly promoted lung metastasis, E-selectin expression in the lungs of mice with ALI or pneumonia was significantly enhanced compared with control mice. Conclusion: Up-regulation of adhesion molecules, but not HGF/c-Met signaling, may contribute to the lung metastasis enhanced by local infection/inflammation.