Inhibition of tumor growth and metastasis by ATF-Fc, an engineered antibody targeting urokinase receptor.
Cancer Biol Ther
; 7(5): 651-9, 2008 May.
Article
en En
| MEDLINE
| ID: mdl-18245952
Urokinase (uPA) and its receptor (uPAR) play an important role in tumor growth and metastasis, and overexpression of these molecules is strongly correlated with poor prognosis in a variety of malignant tumors. In this study, ATF-Fc, an antibody-like molecule comprising the amino-terminal fragment of human uPA (ATF) linked to the Fc fragment of human IgG1 via a flexible linker was developed. Its antitumor activities were evaluated in vitro and in vivo. The results showed that ATF-Fc had obvious cytotoxic effect on several types of tumor cells, which is dependent on cellular expression of uPAR and its Fc fragment. Treatment with ATF-Fc caused a significant suppression on tumor growth and metastasis of xenograft human tumors (MCF-7 breast cancer and BGC-823 gastric cancer) in athymic nude mice. Furthermore, we demonstrated that ATF-Fc had an anti-angiogenesis activity both in vitro and in vivo. In conclusion, we provided a novel therapeutic antibody-like molecule in the management of a variety of solid tumors by disrupting the uPA/uPAR interaction.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fragmentos Fc de Inmunoglobulinas
/
Activador de Plasminógeno de Tipo Uroquinasa
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Receptores de Superficie Celular
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Neoplasias
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cancer Biol Ther
Asunto de la revista:
NEOPLASIAS
/
TERAPEUTICA
Año:
2008
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos