These results, combined with recent studies of the tumor metastasis suppressor gene KAI1 and plasminogen activator inhibitor 1 (PAI1), define a new category of molecular targets of p53 that have the potential to negatively regulate tumor invasion and/or metastasis.
Methylation of a CpG island within the promoter region of the KAI1metastasis suppressor gene is not responsible for down-regulation of KAI1 expression in invasive cancers or cancer cell lines.
There was a significant inverse correlation between KAI1/CD82 expression and regional lymph node metastasis (P = 0.0045), distant metastasis (P = 0.0092), the number of lymph node metastases (P = 0.0019), and pathologic stage (P = 0.0046).
The authors believe that decreased and negative KAI1/CD82 expression in late-stage CaP may be related to tumor progression and metastasis, and appears to be a prognostic marker.
The purpose of this study was to examine whether KAI1/CD82 is expressed in bone and soft tissue tumors, and whether it is associated with metastasis to the lungs.
In addition, tumor suppressor genes such as KAI1 are expressed at reduced levels, thereby enhancing the ability of pancreatic cells to form metastases.
Because metastasis formation is a critical step in tumor progression and a negative prognostic factor, we compared the expression of nm23-H1 and KAI1, two metastasis-suppressing genes, in papilla of Vater cancer and pancreatic cancer.
Northern blot analysis revealed expression of known metastasis-related genes, KAI1 and heparanase, to be decreased in C5F, but no differences in expression of nm23-H1 were evident.
Real-time quantitative RT-PCR showed that the CO-029 mRNA level was 1.7 times higher (P=0.030) in cancerous tissues than in non-cancerous tissues. mRNA expression of the other tetraspanins, CD9 and CD82, was downregulated in HCC, especially in tumors with intrahepatic spreading (portal vein invasion and/or intrahepatic metastasis).
Recently, identification of a sequence with homology to the consensus p53-binding motif in the promoter of the KAI1metastasis suppressor gene, has led to a proposal that transcriptional regulation by p53 controls expression of KAI1, and that a dramatic down-regulation of KAI1 mRNA levels in invasive tumors and many tumor cell lines, is directly due to loss of p53 function.
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.