Cancer Flag May Fight Tumors

A protein that doctors test for as an indication of prostate cancer may actually be used by the body in battling the disease, a study indicates.

Millions of American men get blood tests every year to check for prostate specific antigen. Elevated levels of PSA can indicate the presence of cancer.

"God didn't put PSA as a marker of prostate cancer. There's got to be some biological function of this molecule, and in our minds eye it had not been defined adequately," said Dr. John W. Holaday, one of a team of researchers in Maryland that found evidence that PSA itself may slow the growth of cancer.

"There was data showing that women with advanced breast cancer, who had higher levels of PSA, had a better prognosis," Holaday said. "That taught us two things: that prostate specific antigen is not prostate specific and, secondly, it appears to be collated with an improved outcome."

Some scientists have speculated that it might be possible to slow the progression of prostate cancer by reducing PSA, and there have been attempts to develop an anti-PSA vaccine.

Holaday said his group's results would argue against that.

"Interestingly, no one had ever taken PSA ... and added it to a bunch of prostate cancer cells or other kinds of cancer cells, and made them grow more," he said. "No one really ever asked the question: 'What does PSA do?"'

So his team did the tests.

"Our results suggest that, in addition to its role as an indicator of prostate cancer, PSA may also inhibit the growth of blood vessels associated with cancer progression," the team from EntreMed Inc. of Rockville, Md., reports in the Oct. 6 issue of the Journal of the National Cancer Institute.

"As a man over 50, I know that when my prostate PSA levels are measured on an annual basis. I look to that as a measure of progressive disease or lack thereof," Holaday said.

"But I also realize that when it reaches the later years, often people don't even treat prostate cancer in men 75 years of age and older because it grows so slowly. We think it grows slowly because the PSA it makes keeps it in check."

Cancer researcher Dr. Gerald Murphy of Northwest Hospital's Pacific Northwest Cancer Foundation in Seattle called the result: "very interesting. I had no idea that PSA would have this associated effect."

Murphy said he would need to know more about the type of PSA tested and how it operates, but said the report does help explain the increase in PSA as cancer grows.

Scientists see two fronts in the battle against cancer: attacking the tumor cells themselves and battling the endothelial cells that make up blood vessels to bring the tumor oxygen and nutrients.

The EntreMed scientists have been working on endostatin, a protein that blocks blood-vessel development in tumors. It is currently in the first phase of clinical trials on humans.

After lab tests indicated that PSA added to cancer cells ihibited the formation of new blood vessels, the scientists introduced cancer cells to mice susceptible to lung cancer, and treated some of the mice with PSA.

Mice that had been treated with PSA averaged 62 to 78 tumor nodules in their lungs after 14 days. In contrast, mice that did not receive PSA averaged 99 to 131 tumors. In similar tests using endostatin, treated mice averaged eight to 24 tumors.

PSA is not specific only to prostates, but has also been found in patients with breast, lung and uterine cancers.

Written By Randolph E. Schmid