| Budget Amount *help |
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1996: ¥4,900,000 (Direct Cost: ¥4,900,000)
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| Research Abstract |
In our previous studies we showed that motility related protein-1 (MRP-1) is a glycoprotein recognized by monoclonal antibody (MAb) M31-15, and that the sequence of MRP-1 is identical to that of CD9, a while cell differentiation antigen. Transfection of MRP-1/CD9 cDNA into cultured non-hematopoietic cells suppresses cell motility. The extent of suppression is derectly related to the level of MRP-1/CD9 expression. In addition the metastatic potential of MRP-1/CD9-transfected melanoma cells BL6 is lower than that of control BL6 cells. To determine whether these experimental results are of relevance with respect to actual human tumors, we performed the prospective study of patients with non-small cell lung cancers, breast cancers, pancreatic cancers and colon cancers using quantitative reverse-transcriptase polymerase chain reaction and immunohistochemistry. Of patients with lung cancers, the overall survival rate of the 108 patients (57.7%) with MRP-1/CD9-positive tumors was strikingly h
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igher than that of the 79 patients (42.3%) with MRP-1/CD9-reduced tumors.(57.6% vs.25.9%, p=0.0001). Cox multivariate regression analysis showed that nodal status, and MRP-1/CD9 status were significant factors for a prognosis (p<0.0001 and p=0.0083, respectively). Of 109 patients with breast cancers, 73 tumors (67.0%) were MRP-1/CD9 positive, and 36 tumors (33.0%) were MRP-1/CD9 negative. The discase-free survival rate and the 5-year survival rate of patients with MRP-1/CD9-negative tumors were both significantly lower than patients with MRP-1/CD9-positive tumors (P=0.0005 and P=0.0380, respectively). Cox regression analysis also demonstrated that MRP-1/CD9 status was a significant factor for a prognosis (p=0.0016). In pancreatic cancers, the overall survival rate for the 17 patients whose tumors had reduced MRP-1/CD9 gene expression was strikingly lower than that of the 18 patients with MRP-1/CD9-positive tumors (p=0.0015). In a multivariate analysis using the Cox proportional hazard model, MRP-1/CD9 status was found to be the only significant prognostic factor for survival. However, of patients with colon cancers, no signicicant difference is found due to the short observation time. Our data suggest that low MRP-1/CD9 expression by malignant tumors may be associated with a poor prognosis. On the other hand, sequence analysis with lung cancer revealed that MRP-1/CD9 have the hot spots at codon 143 and 163, both of which change from A to G.The former aminoacid changes are from LYS to ARG,and the latter from ASN to ASP.However, these mutant MRP-1/CD9 DNA transfection had no effect of the functions. Down-regulation due to abnormal promotor rather than mutation may be a more common mechanism in the progression of cancer. Less
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