Expression of HGF/NK4 in ovarian cancer cells suppresses intraperitoneal dissemination and extends host survival

@article{Saga2001ExpressionOH,
  title={Expression of HGF/NK4 in ovarian cancer cells suppresses intraperitoneal dissemination and extends host survival},
  author={Y. Saga and H. Mizukami and M. Suzuki and M. Urabe and A. Kume and T. Nakamura and I. Sato and K. Ozawa},
  journal={Gene Therapy},
  year={2001},
  volume={8},
  pages={1450-1455}
}
Peritoneal dissemination is the most frequent progression pathway of ovarian cancer and is therefore a key step to improve the prognosis. NK4, a large part of the α-chain of hepatocyte growth factor, is known to inhibit cancer cell migration. To characterize the function of NK4 and investigate its potential role in gene therapy of ovarian cancer, we introduced NK4 cDNA to an ovarian cancer cell line HRA and investigated its effects both in vitro and in vivo. HRA cells were transfected with… Expand
Tumor suppression effect using NK4, a molecule acting as an antagonist of HGF, on human gastric carcinomas
TLDR
NK4 is a promising therapeutic agent and its gene delivery may be a new approach to treating patients with advanced gastric cancer, as its gene expression has a potential role in controlling proliferation of cancer cells. Expand
Overexpression of PTEN in ovarian cancer cells suppresses i.p. dissemination and extends survival in mice
TLDR
Overexpression of PTEN suppressed tumor growth and peritoneal dissemination of VEGF-hypersecretory ovarian cancer cells and prolonged the survival time of the mice with peritoneally disseminated tumor. Expand
Hepatocyte growth factor and Met in tumor biology and therapeutic approach with NK4
TLDR
In experimental models of distinct types of cancers, NK4 inhibited Met activation and this was associated with inhibition of tumor invasion and metastasis, andNK4 inhibited tumor angiogenesis, thereby suppressingAngiogenesis‐dependent tumor growth. Expand
Efficient Inhibition of Ovarian Cancer Growth and Prolonged Survival by Transfection with a Novel Pro-Apoptotic Gene, hPNAS-4, in a Mouse Model
TLDR
The promising results on the potential antitumor effects of hPNAS-4 on ovarian cancer in vitro and in vivo may be explained, in part, by the induction of apoptosis and inhibition of angiogenesis. Expand
Growth and angiogenesis of human breast cancer in a nude mouse tumour model is reduced by NK4, a HGF/SF antagonist.
TLDR
It is concluded that NK4 has a significant effect on the growth of human breast tumours in nude mice, particularly when stimulated by HGF/SF or fibroblasts, which gives a clear indication of the therapeutic worth of NK4. Expand
Mechanisms and significance of bifunctional NK4 in cancer treatment.
TLDR
In experimental models of distinct types of cancers, NK4 protein administration or NK4 gene therapy inhibited tumor invasion, metastasis, and angiogenesis-dependent tumor growth, suggesting that cancer treatment with NK4 may prove to suppress malignant tumors to be 'static' in both tumor growth and spreading. Expand
Hepatocyte growth factor enhances ovarian cancer cell invasion through down-regulation of thrombospondin-1
TLDR
HGF is a potential down-regulator of TSP-1, through MAPK signaling pathways, leading to the induction of MMP-9 expression and subsequent invasion of SKOV-3 cells, which enhances the understanding of the mechanisms of signaling transduction in the HGF-induced invasion and progression of ovarian cancer. Expand
HGF–MET Cascade, a Key Target for Inhibiting Cancer Metastasis: The Impact of NK4 Discovery on Cancer Biology and Therapeutics
TLDR
This paper prepared NK4 as an antagonist of HGF: NK4 inhibits HGF-mediated MET tyrosine phosphorylation by competing with HGF for binding to MET. Expand
The hepatocyte growth factor antagonist NK4 inhibits indoleamine-2,3-dioxygenase expression via the c-Met-phosphatidylinositol 3-kinase-AKT signaling pathway
TLDR
Results suggest that NK4 inhibits IDO expression via a c-Met-PI3K-AKT signaling pathway, which enhanced the sensitivity of cancer cells to NK cells in vitro and promoted NK cell accumulation in the tumor stroma in vivo. Expand
Augmented anti-tumor therapy through natural targetability of macrophages genetically engineered by NK4 plasmid DNA
TLDR
It is concluded that the Mφ injected functioned as the natural carrier of tumor targeting for anti-tumor NK4 molecules, resulting in enhanced suppression of tumor growth at a high selectivity. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 28 REFERENCES
Antagonistic effect of NK4, a novel hepatocyte growth factor variant, on in vitro angiogenesis of human vascular endothelial cells.
  • W. Jiang, S. Hiscox, +4 authors R. Mansel
  • Biology, Medicine
  • Clinical cancer research : an official journal of the American Association for Cancer Research
  • 1999
TLDR
Data show that NK4 is a complete antagonist to HGF, which inhibits HGF-induced endothelial movement and tubule formation, which may have an important bearing on the control of cancer progression through its role in angiogenesis. Expand
Inhibition of tumor growth and invasion by a four-kringle antagonist (HGF/NK4) for hepatocyte growth factor
TLDR
HGF/NK4 may inhibit growth and invasion of carcinoma cells, as mediated by HGF during tumor-stromal interactions, and it is proposed that there is a unique therapeutic potential for HGF/ NK4 to prevent tumor invasion and perhaps even metastasis. Expand
Nk4, a new HGF/SF variant, is an antagonist to the influence of HGF/SF on the motility and invasion of colon cancer cells
TLDR
The results show that the ability of HGF/SF to stimulate tumour cell motility and invasion, properties required for metastatic spread, can be inhibited by NK4, which may have an important role in the control of cancer metastasis. Expand
Establishment of a human ovarian cancer cell line capable of forming ascites in nude mice and effects of tranexamic acid on cell proliferation and ascites formation.
TLDR
In injections of tranexamic acid to nude mice treated with cisplatin resulted in a significant inhibition of the ascites formation and prolongation of 50% survival. Expand
Expression of angiostatin cDNA in a murine fibrosarcoma suppresses primary tumor growth and produces long-term dormancy of metastases.
TLDR
This study shows the diminished growth of lung metastases after removal of the primary tumor, suggesting that metastases are self-inhibitory by halting angiogenesis, and may provide a novel approach for cancer therapy by antiangiogenic gene therapy with a specific angiogenic inhibitor. Expand
Induction of hepatocyte growth factor in fibroblasts by tumor-derived factors affects invasive growth of tumor cells: in vitro analysis of tumor-stromal interactions.
TLDR
There are mutual interactions between carcinoma cells and fibroblasts: IL-1, bFGF, and platelet-derived growth factor derived from tumor cells play a role in inducing HGF expression in stromal fibro Blasts, whereas fibroblast-derived HGF, in turn, leads to invasive growth in carcinoma Cells. Expand
A novel strategy for the tumor angiogenesis-targeted gene therapy: Generation of angiostatin from endogenous plasminogen by protease gene transfer
TLDR
Although the selection of more profitable virus vectors and cells to be transduced awaits further studies, such a protease gene transfer strategy may provide a new approach to anti-angiogenesis gene therapy for malignant tumors and their metastasis in vivo. Expand
Acquisition of Invasive Phenotype in Gallbladder Cancer Cells via Mutual Interaction of Stromal Fibroblasts and Cancer Cells as Mediated by Hepatocyte Growth Factor
TLDR
The looped interaction of carcinoma cells and stromal fibroblasts mediated by HGF and a HGF‐inducer such as IL‐1β may be one mechanism which would explain the acquisition of malignant phenotype through tumor‐stromal interactions. Expand
HGF/NK4 is a specific antagonist for pleiotrophic actions of hepatocyte growth factor
TLDR
According to reports, this is the first documentation of a specific antagonist which abrogates the mitogenic, motogenic, and morphogenic activities of HGF. Expand
Adeno-associated virus-mediated delivery of antiangiogenic factors as an antitumor strategy.
TLDR
Rec recombinant adeno-associated virus vectors that carry genes coding for angiostatin, endostatin and an antisense mRNA species against vascular endothelial growth factor (VEGF) efficiently transduced three human tumor cell lines tested. Expand
...
1
2
3
...