Laminar shear stress inhibits high glucose-induced migration and invasion in human bladder cancer cells.

Abstract

High glucose has been known to play a pathogenic role in the development and progression of bladder cancer in diabetics, whereas the leading cause of death in such patients is mainly attributed to hyperglycemia-enhanced metastasis. In addition to the impact of glucose, cancer cells may be affected by laminar shear stress (LSS) generated from interstitial, blood, and/or lymphatic fluid flows during metastasis. Although the effect of flow-induced mechanical force on cancer pathophysiology has been extensively investigated, very little is understood regarding the cells that are simultaneously stimulated by LSS and hyperglycemia. To address this issue, the influence of LSS on bladder cancer cell motility in a hyperglycemic environment was examined. Based on the results of cell movement and protein expression analyses, we found that both cell migration and invasion were up- and downregulated by 25mM glucose and 12 dynes/cm2 LSS, respectively. Furthermore, the motility of the cells with simultaneous hyperglycemic and LSS stimulations was significantly reduced compared with that of the cells stimulated by high glucose alone (P < 0.05), demonstrating that the LSS rather than hyperglycemia played the dominant role in regulation of cell motility. These results implied that LSS with an intensity ≥ 12 dynes/cm2 may serve as a feasible tool to reduce bladder cancer motility in diabetics.