Tumor suppression effect using NK4, a molecule acting as an antagonist of HGF, on human gastric carcinomas
- 24 July 2002
- journal article
- other
- Published by Springer Nature in Cancer Gene Therapy
- Vol. 9 (8) , 700-707
- https://doi.org/10.1038/sj.cgt.7700482
Abstract
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.Keywords
This publication has 24 references indexed in Scilit:
- Targeting Angiogenesis and HGF Function Using an Adenoviral Vector Expressing the HGF Antagonist NK4 for Cancer TherapyMolecular Therapy, 2002
- Expression of HGF/NK4 in ovarian cancer cells suppresses intraperitoneal dissemination and extends host survivalGene Therapy, 2001
- The HGF/SF-Induced Phosphorylation of Paxillin, Matrix Adhesion, and Invasion of Prostate Cancer Cells Were Suppressed by NK4, an HGF/SF VariantBiochemical and Biophysical Research Communications, 2001
- Antisense epidermal growth factor receptor delivered by adenoviral vector blocks tumor growth in human gastric cancerCancer Gene Therapy, 1999
- Hepatocyte growth factor/scatter factor, its molecular, cellular and clinical implications in cancerCritical Reviews in Oncology/Hematology, 1999
- Inhibition of tumor growth and invasion by a four-kringle antagonist (HGF/NK4) for hepatocyte growth factorOncogene, 1998
- Aberrant expression of c‐met mRNA in human gastric carcinomasInternational Journal of Cancer, 1993
- Hepatocyte Growth Factor and Transforming Growth Factor-.BETA. Stimulate both Cell Growth and Migration of Human Gastric Adenocarcinoma Cells.Cell Structure and Function, 1992
- Isolation and expression of cDNA for different forms of hepatocyte growth factor from human leukocyteBiochemical and Biophysical Research Communications, 1990
- Partial purification and characterization of hepatocyte growth factor from serum of hepatectomized ratsBiochemical and Biophysical Research Communications, 1984