In nude mice, after feeding with VP-16, the number of tumors metastasized from spleen to liver was obviously reduced, and KAI1/CD82 protein expression became stronger in those metastatic tumors.
Additionally, advanced and metastasized tumor tissues revealed significantly down-regulated CD82 protein expression (p = 0.033 and p = 0, respectively), which correlated with the tumor pTNM stage (p = 0.001).
In multivariate analysis, high VM, Notch4, DLL4 levels, tumor size, LNM, DM, TNM stage, and low KAI1/CD82 levels were potential to be independent prognostic factors for overall survival time (OST) in NSCLC patients.VM and the expression of Notch4, DLL4, and KAI1/CD82 represent promising markers for tumor metastasis and prognosis, and maybe potential therapeutic targets for NSCLC.
To determine MRP-1/CD9 gene and KA11/CD82 gene expression, which have been postulated to be metastasis suppressor genes, we have applied quantitative RT-PCR.
Moreover, loss of KAI1 expression significantly abrogated NDRG1-mediated metastatic suppression in vitro as well as in a spontaneous metastasis animal model, indicating that KA11 is a functional downstream target of the NDRG1 pathway.
Since the transforming growth factor β (TGF-β) and Wnt signals induce EMT in various epithelial cell types, we examined whether and how the CD82/KAI1metastasis suppressor affects the TGF-β and Wnt signal-dependent EMT in human prostate cancer cells.
We have mapped the human prostate-specific membrane antigen (PSM) gene to the chromosome 11p11.2 region at 62.5 cM, a region which also contains the prostatic cancer metastasis suppressor gene KAI-1.
These results reemphasize the important role of MRP-1/CD9 and KAI1/CD82 in the suppression of the metastatic process and also show the feasibility of gene therapy when using these tetraspanins for lung cancer to prevent metastasis to the regional lymph nodes.
Recent studies suggest that complex mechanisms underlie CD82 loss of function, including altered transcriptional regulation, splice variant production and post-translational protein modifications, and indicate a central role for CD82 in controlling metastasis as a 'molecular facilitator'.