Science

NK4 gene therapy suppresses pancreatic cancer liver metastasis in mice

Last Updated: 2005-10-27 12:15:23 -0400 (Reuters Health)

NEW YORK (Reuters Health) - In mice, adenovirus-mediated NK4 gene transfer to the liver suppresses metastasis of pancreatic cancer to the liver and prolongs life, scientists from Japan report.

These findings "suggest the possibility that adenovirus-mediated (Ad-NK4) can inhibit metastatic liver tumors in postoperative pancreatic cancer patients," Dr. Mitsuhiko Murakami from Kyushu University in Fukuoka and colleagues write in the October 20th International Journal of Cancer.

In an earlier study, the researchers found that hepatocyte growth factor may be involved in the spread of postoperative pancreatic cancer and that NK4, an hepatocyte growth factor fragment, can inhibit metastatic behavior.

Dr. Murakami's group has now shown, in a mouse pancreatic cancer hepatic metastasis model, that intrasplenic injection of recombinant Ad-NK4 induces "high and relatively maintained" expression of NK4 in the liver and suppresses the number and growth of metastatic foci in the liver.

Immunohistochemical analysis of metastatic tumors showed a "remarkable decrease in microvessel density and an increase in the number of apoptotic tumor cells after treatment with Ad-NK4," they further report.

Mice treated with Ad-NK4 survived significantly longer than control mice because, according to the scientists, "tumor growth and dissemination from metastatic liver tumor were inhibited, so the onset of liver dysfunction and intraabdominal bleeding were delayed."

Dr. Murakami and colleagues think the bifunctional nature of NK4 -- as an hepatocyte growth factor antagonist and an angiogenesis inhibitor -- may lead to its development as a key drug in tumor therapy.

Int J Cancer 2005;117:160-165.