Mopping up cancer chemicals

	Murray Korc

Death rates from pancreatic cancer might one day be drastically reduced by a specially designed cell receptor that mops up growth factors released by a tumor.

Murray Korc and his team at the University of California Irvine (UCI) Medical Center believe they can explain the puzzling increase of concentrations of certain chemicals seen in tumor cells; the team's findings could lead to a better treatment for one of the deadliest forms of cancer.

The team investigated whether tumour growth factors could bind to "dummy" receptors - ones that cannot pass on cell signals to their neighbours. When TGF-beta, which is found in many types of cancer cells, binds to the dummies, the result is a reduction in tumor growth of about 72% within one week of injection of the dummy receptor into the tumor. This was also accompanied by a decrease in the spread of cancer cells - metastasis - to other parts of the mouse body. "TGF-beta normally inhibits cell growth," explains Korc, "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." When TGF-beta binds to a receptor that does not pass on the signal to other cells, that receptor simply acts as a sponge, soaking up the growth factor and so reducing its effects. If this phenomenon is found to occur in humans too, it might be used in some way to reduce tumour growth and metastasis.

Metastasis

Pancreatic cancer has only a 20% survival rate after one year for people diagnosed with the disease, according to the American Cancer Society. Chemotherapy and radiation therapy are useful but not 100% while surgery is often thwarted by metastasis.

"This study confirms our earlier findings suggesting that increased levels of TGF-beta make pancreatic cancer cells grow more aggressively," Korc adds. Dummy receptors for tumor necrosis factor (TNF) have already found use in reducing the excessive inflammation of arthritis. The cellular interactions involved in pancreatic cancer and TGF-beta are completely different from those in rheumatoid arthritis, but Korc hopes that the dummy TGF-beta receptor concept may prove as effective in pancreatic cancer. The team is currently working to this end.

Molecular Cancer Therapeutics, 2002, 161-167.