Inhibition of colon cancer growth and metastasis by NK4 gene repetitive delivery in mice

• Published in: Biochemical and biophysical research communications Vol. 358; no. 1; pp. 117 - 123
• Main Authors: Wen, Jinhua, Matsumoto, Kunio, Taniura, Naoko, Tomioka, Daisaku, Nakamura, Toshikazu
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22-06-2007
• Subjects: Animals; Cell Line; Cell Line, Tumor; Cell Movement; Cercopithecus aethiops; Colon cancer; Colonic Neoplasms - blood supply; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Colonic Neoplasms - therapy; Dogs; Gene Transfer Techniques; Hepatocyte Growth Factor - genetics; Hepatocyte Growth Factor - metabolism; HGF; Humans; Liver metastasis; Liver Neoplasms - secondary; Liver Neoplasms - therapy; Met; Mice; Neoplasm Invasiveness; Neoplasm Transplantation; Neovascularization, Pathologic - therapy; NK4; Proto-Oncogene Proteins c-met - antagonists & inhibitors; Tumor angiogenesis; Tumor angiogenesis; Colon cancer; Met; HGF; NK4; Liver metastasis
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2007.04.098

NK4, originally prepared as a competitive antagonist for hepatocyte growth factor (HGF), is a bifunctional molecule that acts as an HGF-antagonist and angiogenesis inhibitor. When the expression plasmid for NK4 gene was administered into mice by hydrodynamics-based delivery, the repetitive increase in the plasma NK4 protein level was achieved by repetitive administration of NK4 gene. Mice were subcutaneously implanted with colon cancer cells and weekly given with the NK4 plasmid. The repetitive delivery and expression of NK4 gene inhibited angiogenesis and invasiveness of colon cancer cells in subcutaneous tumor tissue and this was associated with suppression of primary tumor growth. By fifty days after tumor implantation, cancer cells naturally metastasized to the liver, whereas NK4 gene expression potently inhibited liver metastasis. Inhibition of the HGF-Met receptor pathway and tumor angiogenesis by NK4 gene expression has potential therapeutic value toward inhibition of invasion, growth, and metastasis of colon cancer.