Reuters Health Information (2005-10-27): NK4 gene therapy suppresses pancreatic cancer liver metastasis in mice
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
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
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
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.