MAY 4, 1998

Researchers Discover Cancer Invasion Enzymes In Killer Cells

FORT WORTH, Texas-- A mystery related to how the immune response helps protect against cancer has reached a new level of understanding through research reported from the University of North Texas Health Science Center. The research reveals the presence of two enzymes in a type of white blood cell that are usually found in advanced tumors. The research is published in the May 1 edition of the Journal of Immunology.

Led by Dr. Ronald H. Goldfarb, chairman of the department of molecular biology and immunology at the UNT Health Science Center, this research is the first to show that certain destructive enzymes are produced by white blood cells called activated natural killer cells. These enzymes, known as matrix metalloproteinases (MMPs), are widely known for a very negative role: helping tumor cells spread throughout the body. It now appears that these enzymes might also help cancer-killing white blood cells search out and destroy aggressive tumors.

Natural killer cells recognize and kill tumor cells as the first line of defense of the immune response against cancer. While natural killer cells have the ability to kill tumor cells, they have to first accumulate within the tumor in order to be effective. That’s where the work reported by the Fort Worth-based researchers comes into play. When natural killer cells are stimulated with a protein called interleukin-2, they become activated natural killer cells which have a more lethal effect against cancer cells. They also hunt down malignant tumors with greater speed and certainty. According to Dr. Goldfarb, within 16 hours of the injection, activated natural killer cells are able to migrate out of blood vessels in the tumor and attach to tumor cells where the have a better chance to help destroy the tumor.

“We noted that activated natural killer cells seemed to travel throughout the body like the tumor cells they were trying to kill — that is, they also travel throughout the body and track the tumor cells that spread throughout the body,” said Dr. Goldfarb. “The destructive enzymes of the killer cells may help in this tracking and help lead to the ultimate devastation of the advanced tumors that they invade.”

As reported in this month’s Journal of Immunology , the health science center’s research has implications for the possible develpment of new drug therapies for advanced cancer.

Dr. Goldfarb’s six-year research program, which began at the University of Pittsburgh Cancer Institute, was initially funded by the National Cancer Institute/National Institutes of Health. The American Cancer Society later funded the research grant, the only American Cancer Society research grant in Tarrant County. Dr. Goldfarb plans to establish an Institute for Cancer Research at the health science center in the coming months.

Other investigators in this research include Dr. Richard P. Kitson of the health science center, Dr. Pierette M. Appasamy, University of Pittsburgh School of Medicine; Dr. Ulf Nannmark, University of Göteborg, Sweden; Dr. Per Albertsson, visiting scientist at the health science center also from the University of Göteborg; and Megan K. Gabauer, formerly of the University of Pittsburgh Cancer Institute.