title: Inhibition of tumor growth and metastasis by ATF-Fc, an engineered antibody targeting urokinase receptor.
abstract: 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.
authors.affiliation: Beijing Institute of Biotechnology (BIB), Fengtai District, Beijing, China. hu.xianwen@tsinghua.org.cn
authors.forename: Xian-Wen
authors.initials: XW
authors.lastname: Hu
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Duan
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Gao
authors.forename: Shu-Yuan
authors.initials: SY
authors.lastname: Pan
authors.forename: Yong-Mei
authors.initials: YM
authors.lastname: Li
authors.forename: Yongyi
authors.initials: Y
authors.lastname: Xi
authors.forename: Su-Rong
authors.initials: SR
authors.lastname: Zhao
authors.forename: Liang
authors.initials: L
authors.lastname: Yin
authors.forename: Jin-Feng
authors.initials: JF
authors.lastname: Li
authors.forename: Hui-Peng
authors.initials: HP
authors.lastname: Chen
authors.forename: Chu-Tse
authors.initials: CT
authors.lastname: Wu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000737:chemistry; D045744:Cell Line, Tumor; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry*; D007074:Immunoglobulin G / Q000737:chemistry; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000628:therapy*; D009389:Neovascularization, Pathologic; D011956:Receptors, Cell Surface / Q000737:chemistry*; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator / Q000737:chemistry*
chemical_list: D000906:Antibodies; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; C524898:PLAUR protein, human; C524899:Plaur protein, mouse; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator