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.
Yang
Wei-Hung
WH
Department of Orthopaedic Surgery, China Medical University Beigang Hospital, Yun-Lin County, Taiwan.
Chang
Jung-Tzu
JT
Hsu
Sheng-Feng
SF
Li
Te-Mao
TM
Cho
Der-Yang
DY
Huang
Chun-Yin
CY
Fong
Yi-Chin
YC
Tang
Chih-Hsin
CH
D015153:Blotting, Western; D001859:Bone Neoplasms / Q000378:metabolism*; D001920:Bradykinin / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D002469:Cell Separation; D002813:Chondrosarcoma / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D038982:Integrin alpha2beta1 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000378:metabolism; D018002:Receptors, Bradykinin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism
D038982:Integrin alpha2beta1; D016328:NF-kappa B; D018002:Receptors, Bradykinin; D051745:Protein Kinase C-delta; D010738:Type C Phospholipases; D001920:Bradykinin