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Tumor suppression effect using NK4, a molecule acting as an antagonist of HGF, on human gastric carcinomas
Shuya Hirao1, Yukishige Yamada, Fumikazu Koyama
1First Department of Surgery, Nara Medical University, Kashihara, Japan.
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.
Insights
NK4, an antagonist of hepatocyte growth factor (HGF), significantly inhibited gastric cancer cell growth and tumor volume. Gene delivery of NK4 shows promise as a novel therapeutic strategy for advanced gastric cancer.
Area of Science:
- Oncology
- Molecular Biology
- Gene Therapy
Background:
- Hepatocyte growth factor (HGF) drives cancer malignancy, invasion, and metastasis by mediating tumor-stromal interactions.
- NK4 is a recombinant antagonist of HGF, investigated for its potential to inhibit cancer progression.
Purpose of the Study:
- To evaluate the anti-cancer effects of NK4, both endogenously expressed and exogenously delivered, on human gastric carcinoma TMK1 cells.
- To assess the potential of NK4 gene delivery as a therapeutic approach for advanced gastric cancer.
Main Methods:
- TMK1 cells were transfected with NK4 plasmid to create NK4-expressing cells (T11) for in vitro and in vivo growth evaluation.
- Adenovirus-mediated delivery of NK4 (AdCMV.NK4) was used to assess exogenous NK4 effects on TMK1 cell proliferation and tumor growth in vivo.
Main Results:
- NK4-expressing TMK1 cells (T11) exhibited significant growth inhibition compared to controls, both in vitro and in vivo.
- AdCMV.NK4 infection significantly inhibited TMK1 cell proliferation and reduced tumor volume in vivo compared to control groups.
Conclusions:
- NK4 gene expression demonstrates a significant role in controlling cancer cell proliferation.
- NK4 is a promising therapeutic agent, and its gene delivery represents a potential new treatment strategy for advanced gastric cancer.