2001 Fiscal Year Final Research Report Summary
Suppression of metastasis due to regulation of Aminopeptidase-N
| Project/Area Number |
12470279
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Thoracic surgery
|
|---|
| Research Institution | Tazuke Kofukai Medical Research Institute |
|---|
Principal Investigator |
ISHIDA Hisao Tazuke Kofukai Medical reserch Insutitute Dep. V of Oncology, 医学研究所・第5研究部, 研究員 (40322771)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TAKI Toshihiko Tazuke Kofukai Medical reserch Insutitute Dep. V of Oncology, 第5研究部, 主幹 (60135605)
MIYAKE Masayuki Tazuke Kofukai Medical reserch Insutitute Dep. V of Oncology, 第5研究部, 部長 (90250076)
|
|---|
| Project Period (FY) |
2000 – 2001
|
| Keywords | Aminopeptidase-N / CD13 / metastasis / angiogenesis / HUVEC |
|---|
| Research Abstract |
The aims of this study were to systematically investigate the possible involvement of proteins at the cell surface in controlling cell motility and angiogenesis, and further identify the cell surface molecules involved in malignant tumors. We addressed these issues using functional monoclonal antibodies (MAbs), which inhibit cell motility. In addition, we selected MAb that inhibits human umbilical vein endothelial cell migration and tube formation. We established a murine MAb MH8-11, which inhibits cell motility and in vitro angiogenesis. This epitope was a 165-kD protein and the sequencing analysis revealed that it was almost identical to aminopeptidase N (APN)/cluster of differentiation 13 (CD13). APN/CD13 expression was evaluated in colon cancers from 114 patients. Sixty-seven patients were positive and 47 patients were negative for APN/CD13.The disease-free and overall survival rate for patients with positive APN/CD13 expression tumors was significantly lower than that for patients
… More
with negative APN/CD13 expression tumors (P 0.014, 0.033 ; respectively). Among the 47 node-positive patients, the survival rate of patients with negative APN/CD13 expression was better than that of those with positive APN/CD13 expression. Our data suggest that APN/CD13 is involved in cell motility and angiogenesis in vitro, and the expression of APN/CD13 may thus be a useful indicator of a poor prognosis for node-positive patients with colon cancer. In addition, we investigated the expression of APN/CD13 and the intratumor microvessel density (IMD) in 50 patients with pancreatic carcinoma. APN/CD13 was also significantly associated with an increase of the IMD (p=O.OO2). The median survival time of patients with APN/CD13 expression was significantly shorter than that of patients without APN/ CD13 expression (p=0.009), and multivariate analysis showed that the APN/CD13 status was a significant independent factor (p=0.016). APN/CD13 may be a new prognostic marker for patients with pancreatic carcinoma as well as being an angiogenic factor for this cancer. Less
|
