TY - JOUR
T1 - Intraperitoneal injection of adenovirus-mediated NK4 gene suppresses peritoneal dissemination of pancreatic cancer cell line AsPC-1 in nude mice
AU - Saimura, Michiyo
AU - Nagai, Eishi
AU - Mizumoto, Kazuhiro
AU - Maehara, Naoki
AU - Okino, Hidenobu
AU - Katano, Mitsuo
AU - Matsumoto, Kunio
AU - Nakamura, Toshikazu
AU - Narumi, Kou
AU - Nukiwa, Toshihiro
AU - Tanaka, Masao
N1 - Funding Information:
We thank Shoko Nishio for her excellent technical assistance. This study was supported, in part, by Grant-in-Aid from the Ministry of Education, Science, Sports and Culture of Japan; Pancreas Research Foundation of Japan; and Kyushu University Interdisciplinary Programs in Education and Projects in Research Development. A part of the study was carried out at the Morphology Core, Graduate School of Medical Sciences, Kyushu University.
PY - 2002
Y1 - 2002
N2 - NK4, composed of the N-terminal hairpin and subsequent four-kringle domains of hepatocyte growth factor (HGF), acts not only as a competitive antagonist for HGF but also as a potent angiogenesis inhibitor. This study was designed to assess a therapeutic potential of adenovirus-mediated NK4 gene transfer for disseminated pancreatic cancer cells in the peritoneal lavage of nude mice. We constructed a recombinant adenovirus NK4 (Ad-NK4), which encodes a secretable form of human NK4. In vitro migration of AsPC-1 (human pancreatic cancer cell line) was stimulated by HGF, and it was completely inhibited by Ad-NK4 transfection. Weekly intraperitoneal injections of Ad-NK4 could suppress the development of tumor nodules in a nude mouse peritoneal dissemination model. NK4 expression was detected in the disseminated nodules, liver, pancreas, spleen, and mesenterium. Immunohistochemical study of the disseminated tumors showed a remarkable decrease in microvessel density and an increase in number of apoptotic tumor cells in the Ad-NK4-treated mice. Survival of the Ad-NK4-treated mice was significantly improved. This study indicates that the intraperitoneal transduction of adenovirus- mediated NK4 gene may be a useful therapeutic modality to prevent the development of peritoneal dissemination of pancreatic cancer.
AB - NK4, composed of the N-terminal hairpin and subsequent four-kringle domains of hepatocyte growth factor (HGF), acts not only as a competitive antagonist for HGF but also as a potent angiogenesis inhibitor. This study was designed to assess a therapeutic potential of adenovirus-mediated NK4 gene transfer for disseminated pancreatic cancer cells in the peritoneal lavage of nude mice. We constructed a recombinant adenovirus NK4 (Ad-NK4), which encodes a secretable form of human NK4. In vitro migration of AsPC-1 (human pancreatic cancer cell line) was stimulated by HGF, and it was completely inhibited by Ad-NK4 transfection. Weekly intraperitoneal injections of Ad-NK4 could suppress the development of tumor nodules in a nude mouse peritoneal dissemination model. NK4 expression was detected in the disseminated nodules, liver, pancreas, spleen, and mesenterium. Immunohistochemical study of the disseminated tumors showed a remarkable decrease in microvessel density and an increase in number of apoptotic tumor cells in the Ad-NK4-treated mice. Survival of the Ad-NK4-treated mice was significantly improved. This study indicates that the intraperitoneal transduction of adenovirus- mediated NK4 gene may be a useful therapeutic modality to prevent the development of peritoneal dissemination of pancreatic cancer.
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U2 - 10.1038/sj.cgt.7700504
DO - 10.1038/sj.cgt.7700504
M3 - Article
C2 - 12224019
AN - SCOPUS:0036789558
SN - 0929-1903
VL - 9
SP - 799
EP - 806
JO - Cancer Gene Therapy
JF - Cancer Gene Therapy
IS - 10
ER -
