Protein Found To Slow Tumors

A team of researchers at Boston's Children's Hospital announced a significant victory in the fight against cancer last week with the discovery that a protein produced by cancer cells inhibits the growth of secondary tumors.

The team, which included Medical School Professor of Anatomy and Cellular Biology Dr. Judah M. Folkman, found that a fragment of the protein plasminogen prevents the growth of blood vessels around secondary tumors called metastases.

The team, which also included Dr. Catherine Chen, research fellow in surgery; Marsha Moses, assistant professor of surgery and Yuen W. Shing, assistant professor of surgery; has named the newly-discovered fragment angiostatin.

Metastases are formed when cells released into the blood stream by tumors find their way into other organs of the body and form secondary tumors.

"Most patients die of metastases-related disease," said Patricia Steeg, a molecular biologist at the National Cancer Institute in Bethesda, Md.

The significance of Folkman's finding lies in the protein's ability to inhibit angiogenesis (blood vessel growth), said Noel Bouck, a professor of microbiology and immunology at Northwestern University Medical School. "In order to grow, tumors must produce new blood vessels," she said.

Normally, the body tightly regulates the stimulation and inhibition of new blood vessels. Tumors, however, produce inducers to stimulate the creation of blood vessels near the tumor, and inhibitors which prevent the creation of vessels in distant parts of the body, said Bouck.

"Tumors have the ability to stop the growth of metastases," she said. "I talked to surgeons at Northwestern and they said after they removed tumors, metastases grew."

"[Folkman] realized if one cancer cell produced a little inhibitor, a large tumor produces many," Bouck said.

"[Angiostatin has] been very effective in blocking the growth of metastases in mice," said Dr. Michael S. O'Reilly, a member of the Boston team. "It has reduced primary tumor size by 70 percent or better. Existing metastases become dormant."

Researchers at Children's Hospital say that a purified inhibitor, obtained from the serum and urine of tumor-bearing mice, was found to stop anglogenesis.

William Lane, director of the microchemistry facility in the Biological Laboratories at Harvard, identified the protein by comparing the sequencing of amino acids against a database.

"We found the protein was a small part of the plasminogen molecule," Lane said.

"The discovery represents a whole new way to inhibit cancer growth," O'Reilly said. But he warns that researchers are still years away from clinical use. "By all means we have not cured cancer," he said.

Should plasminogen prove to be effective in clinical trials, the non-toxic protein would augment existing cancer treatments. "Most people discover they have tumors before they come into the doctor's office," Bouck said. "My highest hope has been that surgeons could remove the tumor and prevent tumors that are hidden," she said.

The findings, published in the October 21 edition of Cell have attracted worldwide attention.

"The phone has been ringing off the book," Steeg said. "Labs around the world are probably repeating the experiment."

Colleagues praise Folkman's ground-breaking research.

"This is a beautiful piece of work, very stunning," Bouck said.

"This is an extremely important avenue in cancer research," Steeg said. "Work of this caliber doesn't come around often.

"Tumors have the ability to stop the growth of metastases," she said. "I talked to surgeons at Northwestern and they said after they removed tumors, metastases grew."

"[Folkman] realized if one cancer cell produced a little inhibitor, a large tumor produces many," Bouck said.

"[Angiostatin has] been very effective in blocking the growth of metastases in mice," said Dr. Michael S. O'Reilly, a member of the Boston team. "It has reduced primary tumor size by 70 percent or better. Existing metastases become dormant."

Researchers at Children's Hospital say that a purified inhibitor, obtained from the serum and urine of tumor-bearing mice, was found to stop anglogenesis.

William Lane, director of the microchemistry facility in the Biological Laboratories at Harvard, identified the protein by comparing the sequencing of amino acids against a database.

"We found the protein was a small part of the plasminogen molecule," Lane said.

"The discovery represents a whole new way to inhibit cancer growth," O'Reilly said. But he warns that researchers are still years away from clinical use. "By all means we have not cured cancer," he said.

Should plasminogen prove to be effective in clinical trials, the non-toxic protein would augment existing cancer treatments. "Most people discover they have tumors before they come into the doctor's office," Bouck said. "My highest hope has been that surgeons could remove the tumor and prevent tumors that are hidden," she said.

The findings, published in the October 21 edition of Cell have attracted worldwide attention.

"The phone has been ringing off the book," Steeg said. "Labs around the world are probably repeating the experiment."

Colleagues praise Folkman's ground-breaking research.

"This is a beautiful piece of work, very stunning," Bouck said.

"This is an extremely important avenue in cancer research," Steeg said. "Work of this caliber doesn't come around often.