014-AP-02


Growth of Pancreatic Tumor Cells Reduced; May Increase Survival Rates

Irvine, Calif., Jan. 18, 2002 -- A specially designed cell receptor may reduce death rates from pancreatic and other cancers by sopping up excess tumor-produced chemicals like a sponge, a UCI College of Medicine study has found.

The study, using human cancer cells in mice, helps explain the puzzling increases in certain chemicals seen in tumor cells and may help increase survival rates from pancreatic cancer, currently one of the world's deadliest. The study appears in the January issue of Molecular Cancer Therapeutics.

Dr. Murray Korc, professor of medicine and chief of endocrinology at UCI Medical Center, and his colleagues found that the binding of growth factors to "dummy" receptors--ones incapable of sending signals to cells--sharply reduced tumor sizes and decreased the spread of cancer cells to other parts of the body. The dummy receptors acted like a sponge, mopping up excess levels of the growth factor, known as TGF-beta, found in the cancerous cells.

"TGF-beta normally inhibits cell growth. But it's found at high levels in pancreatic, kidney, liver, breast and other cancer cells, where it increases blood supply to cancer cells and helps them spread," Korc said. "Binding TGF-beta to a receptor that doesn't signal a cell to grow and spread can make that receptor literally sponge up the excess TGF-beta. If this is effective in humans, it may reduce the risk of spreading cancer cells, possibly increasing the chances of survival from pancreatic cancer."

Pancreatic cancer is the world's fourth-deadliest cancer, killing more than 29,000 people in the United States every year. About 30,000 Americans are diagnosed every year. Only 20 percent of those diagnosed survive after one year, according to the American Cancer Society. Chemotherapy and radiation therapy are somewhat effective. Surgical interventions are often thwarted by the fact that 90 percent of pancreatic cancers spread, or metastasize.

The researchers found that mice with the dummy receptor for TGF-beta showed a 72 percent reduction in tumor growth starting one week after injection of the tumor cells, when compared to mice without the receptor. After 50 days, mice with the receptor had an average tumor cell volume of less than 50 cubic millimeters, while mice without the dummy receptor had tumors of about 300 cubic millimeters in size.

In addition, when parts of tumor cells were injected into mice known to show metastatic spreading, those mice with the dummy receptor showed far less evidence of metastasis than mice without the receptor.

Dummy receptors for tumor necrosis factor, also known as soluble TNF receptors, are being used clinically to reduce excessive inflammation in arthritis. These dummy receptors are effective in removing high levels of TNF in rheumatoid arthritis, reducing the severity of the arthritis. While the cellular interactions involved in pancreatic cancer and TGF-beta are completely different from those in rheumatoid arthritis, Dr. Korc hopes that the dummy TGF-beta receptor concept may prove as effective in pancreatic cancer.

"This study confirms our earlier findings suggesting that increased levels of TGF-beta make pancreatic cancer cells grow more aggressively," Korc said. "We were originally surprised to see these high levels of TGF-beta expressed in pancreatic cancer, since it generally inhibits cell growth. If further studies are successful in other animals and in humans, this new role for TGF-beta may lead us to design targeted therapies against pancreatic and other cancers marked by high levels of this growth factor."

Korc and his colleagues, who have been exploring the roles played by TGF-beta and other chemicals for more than 11 years, are now looking at how the dummy TGF-receptor may be developed into an effective treatment.

Korc's colleagues include Melissa Rowland-Goldsmith, Haruhisa Maruyama, Kei Matsuda, Takenao Idezawa, Monica Ralli and Sonia Ralli from UCI. Korc's research was assisted by a grant from the National Cancer Institute. Rowland-Goldsmith also received a postdoctoral fellowship of the George E. Hewitt Foundation for Medical Research.

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Contact:
Andrew Porterfield
(949) 824-3969
amporter@uci.edu

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