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

Gene Therapy volume 8, pages 1450–1455 (2001)Cite this article

Abstract

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 either NK4 or luciferase-expression plasmids. After selection, NK4-expressing HRA cells (HRA/NK4) and the control cells (HRA/LUC) were obtained. NK4 was detected in the culture supernatant of HRA/NK4 by Western analysis. Migration capabilities of the cells were evaluated in vitro by scratch wound healing assay. The number of migrated cells was significantly smaller in the HRA/NK4 cultures than that in the control cultures (HRA or HRA/LUC). Also, the culture supernatant of HRA/NK4 significantly suppressed migration of control cells. This suppressive effect was observed when NK4-expressing cells were mixed with control cells at the ratio of 25% or more. In the in vivo experiments, HRA transfectants were injected intraperitoneally. The number of intraperitoneal tumors of HRA/NK4 was much smaller than that of control. In mice injected with HRA/NK4, ascites formation was suppressed and the survival was significantly prolonged. These findings suggest that NK4-mediated gene therapy can improve the prognosis of ovarian cancer by suppressing peritoneal dissemination. Gene Therapy (2001) 8, 1450–1455.

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Acknowledgements

This work was supported in part by grants from the Ministry of Health, Labor and Welfare of Japan, and the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Jichi Medical School, Yakushiji, Minamikawachi, Tochigi, Japan

    Y Saga, M Suzuki & I Sato

  2. Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical School, Yakushiji, Minamikawachi, Tochigi, Japan

    Y Saga, H Mizukami, M Urabe, A Kume & K Ozawa

  3. Division of Biochemistry, Department of Oncology, Biomedical Research Center, Osaka University Medical School, Suita, Osaka, Japan

    T Nakamura

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  1. Y Saga
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Saga, Y., Mizukami, H., Suzuki, M. et al. Expression of HGF/NK4 in ovarian cancer cells suppresses intraperitoneal dissemination and extends host survival. Gene Ther 8, 1450–1455 (2001). https://doi.org/10.1038/sj.gt.3301553

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