[Growth suppression of subcutaneous tumor by CT26 expressing NK4 in syngeneic mice].
An HGF antagonist, NK4, inhibits not only invasion and metastasis of tumor cells driven by HGF-Met receptor binding, but also tumor angiogenesis. To address the antitumor activities of NK4, we investigated the biological behaviors of CT26 transfected with the NK4 gene (CT26-NK4) in vitro and in vivo. In the in vitro assay, the invasion in MOCK transfected cells (control) was stimulated by HGF; however, in CT26-NK4 cells, these effects were completely inhibited. In the in vivo assay, the tumor growth of CT26-NK4 was strongly suppressed and the survival of CT26-NK4 tumor-bearing mice was significantly prolonged. Immunohistochemical analysis revealed that while proliferating cells (PCNA immunostaining) of CT26-NK4 tumors were weakly suppressed, the micro-vessel number (CD31/PECAM-1 immunostaining) in those tumors was significantly suppressed as compared with the control tumors. In conclusion, NK4 exerts potent antitumor effects via anti-angiogenesis rather than inhibition of biological events of tumor cells stimulated by HGF.
Kubota
Takeshi
T
Dept. of Digestive Surgery, Kyoto Prefectural University of Medicine.
Fujiwara
Hitoshi
H
Amaike
Hisashi
H
Takashima
Kazuhiro
K
Inada
Satoshi
S
Atsuji
Kiyoto
K
Yoshimura
Mamoru
M
Matsumoto
Kunio
K
Nakamura
Toshikazu
T
Yamagishi
Hisakazu
H
D020533:Angiogenesis Inhibitors; D000818:Animals; D017228:Hepatocyte Growth Factor / Q000819:agonists* / Q000235:genetics*; D051379:Mice; D008934:Mitogens; D009374:Neoplasms, Experimental / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D014162:Transfection; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; C066855:HGF protein, human; D008934:Mitogens; D018809:Proliferating Cell Nuclear Antigen; D017228:Hepatocyte Growth Factor