Bradykinin enhances cell migration in human chondrosarcoma cells through BK receptor signaling pathways.

Bradykinin (BK) is an inflammatory mediator, and shows elevated levels in regions of severe injury and inflammatory diseases. BK has recently been shown to be involved in carcinogenesis and cancer progression. In this study, we found that BK increased the migration and the expression of alpha2beta1 integrin in human chondrosarcoma cells. We also found that human chondrosarcoma tissues had significantly higher expression of the B1 and B2 receptors comparing to normal cartilage. BK-mediated migration and integrin up-regulation was attenuated by B1 and B2 BK receptor siRNA or antagonist. Activations of phospholipase C (PLC), protein kinase Cdelta (PKCdelta), and NF-kappaB pathways after BK treatment was demonstrated, and BK-induced integrin expression and migration activity was inhibited by the specific inhibitor of PLC, PKCdelta, and NF-kappaB cascades. Taken together, our results indicated that BK enhances the migration of chondrosarcoma cells by increasing alpha2beta1 integrin expression through the BK receptors/PLC/PKCdelta/NF-kappaB signal transduction pathway.