TY - JOUR
T1 - Gene transduction of NK4, HGF antagonist, inhibits in vitro invasion and in vivo growth of human pancreatic cancer
AU - Maehara, Naoki
AU - Nagai, Eishi
AU - Mizumoto, Kazuhiro
AU - Sato, Norihiro
AU - Matsumoto, Kunio
AU - Nakamura, Toshikazu
AU - Narumi, Ko
AU - Nukiwa, Toshihiro
AU - Tanaka, Masao
N1 - Funding Information:
We thank Shoko Nishio (Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University) for 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.
PY - 2002
Y1 - 2002
N2 - In this study, we investigated the therapeutic effects of adenovirally-mediated transfer of the sequence of NK4, an antagonist for hepatocyte growth factor (HGF), against human pancreatic carcinoma. HGF has been implicated to play an important role in invasion and metastasis of various human cancers through tumor-stromal interactions. Although NK4 has been shown to block the metastatic behavior of cancer cells, problems with cellular delivery of NK4 must be addressed before it can be used for clinical trials. The effects of NK4 gene transduction mediated by recombinant adenovirus (Ad-NK4) were evaluated in a human pancreatic cancer cell line (SUIT-2) by in vitro scattering assays, invasion assays, and subcutaneous transplantation in nude mice. NK4 transduction markedly inhibited scattering and invasion of SUIT-2 cells stimulated by HGF without affecting cell proliferation in vitro. Furthermore, Ad-NK4 significantly inhibited the growth of tumors transplanted to nude mice. The tumor reduction induced by Ad-NK4 was associated with a decreased number of blood vessels surrounding the tumors. These findings suggest that Ad-NK4 gene therapy may be a unique and promising strategy for the treatment of pancreatic cancer.
AB - In this study, we investigated the therapeutic effects of adenovirally-mediated transfer of the sequence of NK4, an antagonist for hepatocyte growth factor (HGF), against human pancreatic carcinoma. HGF has been implicated to play an important role in invasion and metastasis of various human cancers through tumor-stromal interactions. Although NK4 has been shown to block the metastatic behavior of cancer cells, problems with cellular delivery of NK4 must be addressed before it can be used for clinical trials. The effects of NK4 gene transduction mediated by recombinant adenovirus (Ad-NK4) were evaluated in a human pancreatic cancer cell line (SUIT-2) by in vitro scattering assays, invasion assays, and subcutaneous transplantation in nude mice. NK4 transduction markedly inhibited scattering and invasion of SUIT-2 cells stimulated by HGF without affecting cell proliferation in vitro. Furthermore, Ad-NK4 significantly inhibited the growth of tumors transplanted to nude mice. The tumor reduction induced by Ad-NK4 was associated with a decreased number of blood vessels surrounding the tumors. These findings suggest that Ad-NK4 gene therapy may be a unique and promising strategy for the treatment of pancreatic cancer.
UR - http://www.scopus.com/inward/record.url?scp=0036345115&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036345115&partnerID=8YFLogxK
U2 - 10.1023/A:1016395316362
DO - 10.1023/A:1016395316362
M3 - Article
C2 - 12198770
AN - SCOPUS:0036345115
SN - 0262-0898
VL - 19
SP - 417
EP - 426
JO - Clinical and Experimental Metastasis
JF - Clinical and Experimental Metastasis
IS - 5
ER -
