No influence of tumor growth by intramuscular injection of hepatocyte growth factor plasmid DNA: safety evaluation of therapeutic angiogenesis gene therapy in mice.
Recently, a novel therapeutic treatment for ischemic diseases using angiogenic growth factors to augment collateral artery development has been proposed. As intramuscular injection of naked human hepatocyte growth factor (HGF) plasmid DNA induced therapeutic angiogenesis in several animal test subjects, we have started a clinical trial to treat peripheral arterial disease. However, one might assume that over-expression of angiogenic growth factors could enhance tumor growth. To resolve this issue, we examined the over-expression of HGF in tumor bearing mice. Tumors on their backs were prepared with an intradermal inoculation of A431, human epidermoid cancer cells expressing c-Met. These mice were intramuscularly injected with human HGF plasmid or control plasmid into the femoral muscle. Human HGF concentration was increased only in the femoral muscle, but not in blood. Although recombinant HGF stimulated the growth of A431 cells in vitro, temporally and locally HGF elevation in hindlimb had no effect on tumor growth in mice.
Matsuki
Atsushi
A
Division of Gene therapy Science, Biomedical Research Center, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Yamamoto
Seiji
S
Nakagami
Hironori
H
Aoki
Motokuni
M
Tamai
Katsuto
K
Matsumoto
Kunio
K
Nakamura
Toshikazu
T
Ogihara
Toshio
T
Kaneda
Yasufumi
Y
Morishita
Ryuichi
R
D000818:Animals; D016466:CHO Cells; D002455:Cell Division / Q000235:genetics; D045744:Cell Line, Tumor; D006224:Cricetinae; D004247:DNA / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics; D005069:Evaluation Studies as Topic; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D006614:Hindlimb; D006801:Humans; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D008156:Luciferases / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control / Q000628:therapy*; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D014018:Tissue Distribution; D014162:Transfection
D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; D004247:DNA; D008156:Luciferases