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MET, a c-met proto-oncogene product and hepatocyte growth factor (HGF) receptor, is known to play an important role in cancer progression, including bone metastasis. In a previous study, we reported increased expression of MET and matriptase, a novel activator of HGF, in bone metastasis. In this study, we employed a mouse model of renal cell carcinoma (RCC) bone metastasis to clarify the significance of the HGF/MET signaling axis and the regulator of HGF activator inhibitor type-2 (HAI-2). Luciferase-transfected 786-O cells were injected into the left cardiac ventricle of mice to prepare the mouse model of bone metastasis. The formation of bone metastasis was confirmed by whole-body bioluminescent imaging, and specimens were extracted. Expression of HGF/MET-related molecules was analyzed. Based on the results, we produced HAI-2 stable knockdown 786-O cells, and analyzed invasiveness and motility. Expression of HGF and matriptase was increased in bone metastasis compared with the control, while that of HAI-2 was decreased. Furthermore, we confirmed increased phosphorylation of MET in bone metastasis. The expression of matriptase was upregulated, and both invasiveness and motility were increased significantly by knockdown of HAI-2. The significance of ligand-dependent MET activation in RCC bone metastasis is considered, and HAI-2 may be an important regulator in this system.

This study describes a method of evaluating the level of service of road networks, based on the average travel time and travel time reliability using electronic toll collection (ETC) data. The authors focused on the variance in travel time under normal circumstances, thus, traffic accidents were removed from the database, and any effect of individual vehicle preference was excluded. They evaluated the travel time distribution based on the average travel time from ETC data for each 15-min interval. The level of service in an actual intercity highway network was analysed using the proposed method. This analysis showed that the level of service fluctuated according to the road section analysed, the month and the time of day. These findings were confirmed by the shape of the cumulative distribution and indices of average travel time and travel time reliability. Using the evaluation method described here, the analysis also confirmed the change in travel time distribution between major interchanges after the opening of a new intercity highway route. As a great change in the traffic conditions occurred, the authors analysed the relationship between traffic demand and the level of service using detector data.