1. Inhibition of APN/CD13 leads to suppressed progressive potential in ovarian carcinoma cells
- Author
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Hiroaki Kajiyama, Shigehiko Mizutani, Fumitaka Kikkawa, Kazuhiko Ino, Akihiro Nawa, Kiyosumi Shibata, and Mikio Terauchi
- Subjects
Cancer Research ,medicine.medical_specialty ,animal structures ,endocrine system diseases ,Cell ,CD13 Antigens ,lcsh:RC254-282 ,Mice ,Cell Movement ,Leucine ,Cell Line, Tumor ,Internal medicine ,Ovarian carcinoma ,Genetics ,medicine ,Animals ,Humans ,Secretion ,Cell Proliferation ,Ovarian Neoplasms ,Mice, Inbred BALB C ,Metalloproteinase ,business.industry ,Transfection ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,female genital diseases and pregnancy complications ,Endocrinology ,medicine.anatomical_structure ,Oncology ,Tumor progression ,Cell culture ,Disease Progression ,Cancer research ,Matrix Metalloproteinase 2 ,Female ,Stem cell ,business ,hormones, hormone substitutes, and hormone antagonists ,Research Article - Abstract
Background Aminopeptidase N (APN/CD13), a 150-kDa metalloprotease, is a multifunctional cell surface aminopeptidase with ubiquitous expression. Recent studies have suggested that APN/CD13 plays an important role in tumor progression of several human malignancies. In the current study, we investigated the role of APN/CD13 in ovarian carcinoma (OVCA) progression. Methods We first examined the expression of APN/CD13 at the protein level in a variety of OVCA cell lines and tissues. We subsequently investigated whether there was a correlation between APN/CD13 expression and invasive potential of various OVCA cell lines. Moreover, we investigated the function of APN/CD13 in OVCA cells using bestatin, an APN/CD13 inhibitor, or transfection of siRNA for APN/CD13. Results We confirmed that APN/CD13 was expressed in OVCA tissues and cell lines to various extents. There was a positive correlation between APN/CD13 expression and migratory potential in various OVCA cell lines with accordingly enhanced secretion of endogenous MMP-2. Subsequently, we found a significant decrease in the proliferative and migratory abilities of OVCA cells after the addition of bestatin or the inhibition of APN/CD13 expression by siRNA. Furthermore, in an animal model, daily intraperitoneal administration of bestatin after inoculation of OVCA cells resulted in a decrease of peritoneal dissemination and in prolonged survival of nude mice. Conclusion The current data indicate the possible involvement of APN/CD13 in the development of OVCA, and suggest that clinical use of bestatin may contribute to better prognosis for ovarian carcinoma patients.
- Published
- 2007