July 5, 2001 Researchers at Jefferson Medical College and Jefferson's Kimmel Cancer Center have found that a receptor for a bacterial toxin on the surface of metastatic colorectal cancer cells actually controls the growth of the cells. What's more, when the toxin hooks up with the receptor, metastatic colorectal cancer cell growth slows considerably. The scientists believe the receptor-toxin combination could eventually be used with chemotherapy or other agents to slow the advance of the disease.
"Cancer then becomes a chronic disease," says Scott Waldman, M.D., Ph.D., Samuel M.V. Hamilton Family Professor of Medicine and director of the Division of Clinical Pharmacology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, who, along with Giovanni Pitari, M.D., Ph.D., assistant professor of medicine at Jefferson Medical College, led the work. They report their findings July 3 in the Proceedings of the National Academy of Sciences.
Several years ago Dr. Waldman's team discovered the existence of a protein marker, GCC, on the surface of colorectal cancer cells that allows scientists to detect if cells have spread to other areas of the body and where, he says, "they don't belong." GCC can be used as a diagnostic tool to stage patients and to follow them after their surgery to see if their cancer has returned. It turns out that GCC is also a receptor for a bacterial toxin, ST, the cause of traveler's diarrhea.
"Because it's a receptor that sits on the cancer cell surface, when these cells become metastatic, they go to places where the normal tissue doesn't make this receptor," Dr. Waldman explains. "GCC - and the cancer - can be targeted using the bacterial toxin to the receptor."
As a result, GCC is particularly useful. The scientists are testing the receptor as a target for imaging agents to find where in the body metastatic cancer has gone. It also can be used therapeutically, says Dr. Waldman, by coupling cell-killing drugs to the toxin, then homing in on the cancer. GCC is a potential target at which to shoot so-called guided cellular missiles.
Drs. Pitari and Waldman, in anticipation of beginning studies to examine this ST targeting of therapeutics to GCC on colorectal tumors, decided to look at colorectal cancer cells in the laboratory to see if ST itself actually had an effect on the cells.
They were astounded to find that GCC actually regulated the growth of colorectal cancer cells, and that treating the cells with ST didn't kill cancer cells, but rather lengthened the time of the cell growth cycle, slowing the cells' growth and spread.
The researchers think they can take advantage of this "cytostatic," or cell growth-slowing action. "We may be able to use ST as a therapeutic hormone to slow down cancer growth," says Dr. Pitari. "Or we may use ST or another ligand that binds to GCC in combination with another agent to keep tumors at bay." Their next step is to continue their laboratory studies and look into new agents that may work in combination with GCC.
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