Analysis of the function of Aminopeptidase N and neutral and peptidase and application of its cancer therapy.

我们已经established the monoclonal antibody(MAb) MH8-11 suppressing angiogenesis and the cloning ofthis antibody reveals Aminopeptidase N(APN)/CD13. The APN transfected B16-F1 gained a potentialability of metastasis to the lung. Using the actual clinical specimens of lung cancer，colon cancer and pancreatic cancer我们发现APN had an association with angiogenesis，and was a significant factor of poor prognosis. On the其他hand，我们suppose neutral endopeptidase (NEP)/CD10 has anything to do with APN，but the evaluation of clinical specimens showed that NEP is a significant factor for good prognosis。mh75 MAb which we have established also recognized APN. Western blotting with mh75 showed bothl6OkDa and l2OkDa bands但只有150kDa band was detected using n8 -11. The modification of The sugar chain resulted in suchchanges,thus currently it is studied which kinds of sugar chain changes might with the tumorOne of our aims was to identify regulator genes of APN gene，这是唯一确定NEP positive and APN negative的表pression of NEP was decreased in the NEP positive APN negativecell lines. Therefore，the identification of the gene which regulates APN gene remains unknown.使用F1cell line withhighly metastatic potential to the lung，我们投资于the anti-APN MAb could prevent the lung metastasis or not. the number ofmetastatic colony of MH8-11MAb injected group were 41.4±24.4，compared to 98.3 a 41.8 in control. This experiment demonstrated that MH8-11MAb efficiently preventedF1 pulmonary metastasis of (p=0.0043). Currently, as molecular targeting therapy，我们将投资于人类MH8-11可能会支持癌症进展或metastasis.我们此外，投资无论本身是否已提供了一项支持或不支持的进展。

We have established the monoclonal antibody(MAb) MH8-11 suppressing angiogenesis and the cloning of this antibody reveals Aminopeptidase N(APN)/CD13. The APN transfected B16-F1 gained a potential ability of metastasis to the lung. Using the actual clinical specimens of lung cancer, colon cancer and pancreatic cancer, we found that the expression of APN had an association with angiogenesis, and was a significant factor of poor prognosis. On the other hand, we suppose neutral endopeptidase (NEP)/CD10 has anything to do with APN, but the evaluation of clinical specimens showed that NEP is a significant factor for good prognosis. MH7-5 MAb which we have established also recognized APN. Western blotting with MH7-5 showed both l6OkDa and l2OkDa bands, but only 150kDa band was detected using NH8-11. The modification of the sugar chain resulted in such changes, thus currently it is studied which kinds of sugar chain changes might associate with the tumor metastasis. One of our aims was to identify regulator genes of APN gene, and it was only observed that expression of NEP was decreased in the NEP positive and APN negative cell lines. Therefore, the identification of the gene which regulates APN gene remains unknown. Using the F1cell line with highly metastatic potential to the lung, we investigated whether the anti-APN MAb could prevent the lung metastasis or not. The number of metastatic colony of MH8-11MAb injected group were 41.4±24.4, compared to 98.3ア41.8 in control. This experiment demonstrated that MH8-11MAb efficiently prevented the pulmonary metastasis of F1 (p=0.0043). Currently, as the molecular targeting therapy, we will investigate whether human MH8-11 MAb might suppress the cancer progression or metastasis. We also investigate whether the NEP itself has a suppression of progression or not.