| Background: The tetraspanin KAI1/CD82 was identified as a tumor metastasis suppressor that downregulated in various malignant cell types.However,the function of CD82 and its underlying anti-metastasis role in renal cell carcinoma(RCC)is still unraveled.Here,we investigated the expression of CD82 in RCC and explored its regulatory mechanism in RCC cell lines.Methods: CD82 m RNA expression was detected in 30 pairs of RCC tissues and non-tumorous tissues by q RT-PCR method.CD82 protein expression was assessed in 4 pairs of RCC tissues and normal tissues by immunoblotting and 133 cases of RCC samples in a tissue microarray by immunohistochemistry.Transwell migration and invasion assay were conducted to determine the tumor suppressor function after overexpress or knockdown of CD82 in Caki-1 and 786-O cells by overexpression lentiviruses and small interfering RNA(si RNA).Results: CD82 was down-regulated in RCC tissues and RCC cells.CD82 protein expression was 25.6%(34/133)and its expression was significantly associated with histological grade(p=0.041),tumour stage(p=0.036)and tumor size(p=0.020).The migration and invasion of Caki-1 cells were remarkably suppressed in vitro by CD82 overexpression.The migration and invasion ability of 786-O was enhanced by inhibition of CD82.Subsequently,western blot was performed to identify theinfluence of CD82 on TGF-? 1/Smad signaling pathway in RCC.Further experiments with TGF-? stimulation suggested that CD82 may exert its inhibitory role through TGF-? pathway.Conclusion: These results suggest that CD82 played a inhibitory role in RCC metastasis and we first revealed the CD82/TGF-?1/Smad signaling pathway in RCC which may provide novel insight into the mechanisms of RCC metastasis and facilitate the development of new therapeutics against RCC. |
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