Tumor suppression effect using NK4, a molecule acting as an antagonist of HGF, on human gastric carcinomas.
Hepatocyte growth factor (HGF) is involved in malignant behavior of cancers as a mediator of tumor-stromal interactions, facilitating tumor invasion and metastasis. We have investigated whether a blockade of HGF using recombinant NK4, an HGF antagonist, would lead to growth inhibition of the human gastric carcinoma cell line, TMK1. To evaluate the function of endogenous NK4 and investigate its potential inhibitory effect, TMK1 cells were transfected with NK4 plasmid. After selection, NK4-expressing cells (T11) were obtained, and cell growth was evaluated. Significant growth inhibition was observed in the T11-group compared to the control both in vitro and in vivo. Moreover, we investigated the effect of exogenous NK4 transferred by an adenovirus vector (AdCMV.NK4). Cell proliferation of AdCMV.NK4 infected TMK1 cells was significantly inhibited compared with the control group. We also assessed the in vivo tumor suppression effect of AdCMV.NK4. The tumor volume following treatment with AdCMV.NK4 was significantly inhibited compared to that of the control group. These findings indicate that NK4 gene expression has a potential role in controlling proliferation of cancer cells. In conclusion, NK4 is a promising therapeutic agent and its gene delivery may be a new approach to treating patients with advanced gastric cancer.
First Department of Surgery, Nara Medical University, Kashihara, Japan.
Shuya
S
Hirao
Yukishige
Y
Yamada
Fumikazu
F
Koyama
Heisuke
H
Fujimoto
Yasushi
Y
Takahama
Masato
M
Ueno
Kiyoshi
K
Kamada
Takashi
T
Mizuno
Makoto
M
Maemondo
Toshihiro
T
Nukiwa
Kunio
K
Matsumoto
Toshikazu
T
Nakamura
Yoshiyuki
Y
Nakajima
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016466:CHO Cells; D002455:Cell Division / Q000235:genetics; D006224:Cricetinae; D003587:Cytomegalovirus / Q000235:genetics; D005822:Genetic Vectors; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors* / Q000235:genetics*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008934:Mitogens; D013274:Stomach Neoplasms / Q000473:pathology / Q000628:therapy*; D014162:Transfection; D014407:Tumor Cells, Cultured
C066855:HGF protein, human; D008934:Mitogens; D017228:Hepatocyte Growth Factor