Anti-Progressive Effect of Neutral Endopeptidase 24.11 (NEP/CD10) on Cervical Carcinoma in vitro and in vivo
| Autor: | Kiyosumi Shibata, Kazuhiko Ino, Fumitaka Kikkawa, Mikio Terauchi, Hiroaki Kajiyama, Shigehiko Mizutani |
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| Rok vydání: | 2005 |
| Předmět: |
Cancer Research
medicine.medical_specialty Time Factors Blotting Western Mice Nude Uterine Cervical Neoplasms Antineoplastic Agents Biology Transfection Mice Nude mouse Cell Movement In vivo Cell Line Tumor Internal medicine medicine Animals Humans Neoplastic transformation Autocrine signalling Neprilysin Cell Proliferation fungi General Medicine Flow Cytometry biology.organism_classification Immunohistochemistry In vitro Endocrinology Oncology Tumor progression Disease Progression Cancer research Female Plasmids |
| Zdroj: | Oncology. 69:52-62 |
| ISSN: | 1423-0232 0030-2414 |
| Popis: | Objectives: Neutral endopeptidase 24.11 (NEP) is known to play important roles in the maintenance of homeostasis or in neoplastic transformation and tumor progression in certain human malignancies through the enzymatic inactivation of bioactive peptides such as endothelin-1 (ET-1), angiotensin-II, and bombesin. Methods: In this study, we first investigated NEP expression in cervical carcinoma by immunohistochemical staining and Western blot analysis. Next, we examined NEP functions in vitro and in vivo by generating NEP-overexpressing cervical carcinoma cells. Results: We found a significant decrease in cellular proliferative and invasive abilities with a reduced ET-1 concentration in the conditioned medium by NEP overexpression in cervical carcinoma CaSki cells, which have an ET-1 autocrine loop. In addition, these potentials were cancelled by blockade of NEP activity with a specific inhibitor. Although vector-transfected CaSki cells could grow even in serum-free media, NEP-overexpressing cells failed to proliferate in these media. Furthermore, we demonstrated that NEP suppressed tumor formation of subcutaneous xenografts using nude mice. Conclusions: Our results indicated that NEP functions as a tumor-suppressor gene in cervical carcinoma cells, and its expression may have prognostic significance. Further elucidation of the mechanism underlying the observed effect of NEP will contribute to a better understanding of its role in the pathophysiology of cervical carcinoma. |
| Databáze: | OpenAIRE |
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