Expression of hgf/nk4 in ovarian cancer cells suppresses intraperitoneal dissemination and extends host survival

Expression of hgf/nk4 in ovarian cancer cells suppresses intraperitoneal dissemination and extends host survival

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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. Access through your institution Buy or subscribe This is a


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Welfare of Japan, and the Ministry of Education, Culture, Sports, Science and Technology of Japan. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Obstetrics and Gynecology,


Jichi Medical School, Yakushiji, Minamikawachi, Tochigi, Japan Y Saga, M Suzuki & I Sato * 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 * Division of Biochemistry, Department of Oncology, Biomedical Research Center, Osaka University


Medical School, Suita, Osaka, Japan T Nakamura Authors * Y Saga View author publications You can also search for this author inPubMed Google Scholar * H Mizukami View author publications You


can also search for this author inPubMed Google Scholar * M Suzuki View author publications You can also search for this author inPubMed Google Scholar * M Urabe View author publications


You can also search for this author inPubMed Google Scholar * A Kume View author publications You can also search for this author inPubMed Google Scholar * T Nakamura View author


publications You can also search for this author inPubMed Google Scholar * I Sato View author publications You can also search for this author inPubMed Google Scholar * K Ozawa View author


publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download citation * Received: 06 November 2000 * Accepted: 30 June 2001 * Published: 11 October 2001 * Issue Date: 01 October 2001 * DOI:


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currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * NK4 * ovarian cancer * cell migration * peritoneal


dissemination * HGF