| dc.description.abstract | Hyperglycemia has been widely demonstrated as one of major risk factors for tumor deterioration such as tumor metastasis. However, the definite mechanism of how glucose affects tumor development in vivo remains unclear since the interstitial fluid; one of key physiological factors in cellular microenvironment, is usually ignored in most of prior in vitro studies. To address the above issue, in this study, we aimed to investigate the effectiveness of interstitial fluid-induced laminar shear stress (LSS) on human urinary bladder transitional cell carcinoma (BFTC-905), in respects of cellular migration and invasion, in the presence of high glucose concentration. Based on the results of Giemsa and Calcein-AM staining assays, we found that the cells with 25-mM glucose for 24 h exhibited 2.03-fold enhanced migration efficiency (P < 0.01), while the migrated cell number with 12 dynes/cm2 LSS for 4 h significantly decreased ~63% (P < 0.01) as compared with the one without glucose. On the other hand, the migrated cell number with both LSS (12 dynes/cm2) and high glucose (25 mM) is significantly decreased 63% (P < 0.01) as compared to the group treated with glucose alone, indicating that high glucose promotes cellular migration while it was inhibited by LSS. Furthermore, our data showed that the cells with 25-mM glucose for 24 h exhibited 3.6-fold (P < 0.01) enhanced invasive cell number rate, while the invasive cell number with 12 dynes/cm2 LSS for 4 h is not significant difference as compared with the one without glucose. Moreover, the invasive cell number of the BFTC-905 treated with both LSS and 25-mM glucose significantly decreased 59% as compared to the group with glucose alone. According to the Western blot analyses, we investigate the mechanism of tumor metastasis caused by synergistic effect of LSS and glucose, expressions of AKT, Cav-1 and MT1-MMP were examined. We found that expressions of both p-AKT and p-Cav-1 exhibited significantly enhanced (P < 0.01) with glucose alone, and the expressions of MT1-MMP decreased slightly. Augmented along with exposure of LSS only that the expressions of p-AKT is no significant difference, whereas LSS enabled to further decreased the p-Cav-1 (P < 0.05) but increased the MT1-MMP (P < 0.01) expression. However, the results that the expressions of p-AKT and p-Cav-1 with both LSS and glucose exhibited significant decreased, the results show that LSS has an inhibitory effect on the regulation of p-AKT and p-Cav-1 in bladder cancer cells with a high glucose environment. In addition to the expressions of MT1-MMP significant decreased with both LSS and high glucose. In our study show that cell migration of bladder cancer decreased significantly under the laminar shear stress (12 dynes/cm2) in the high glucose environment, and through the Cav-1 pathway regulate the AKT. The tumor invasion also has a decreased significantly, but it′s the less relevant with the laminar shear stress. We suppose that MT1-MMP maybe have affected by other pathways. These results showed that the LSS of tumor metastasis in bladder cancer cells suggest that mechanical microenvironment of tumor cells may play important roles, and it should be taken into account in tumor therapy and management. | en_US |