BOSTON New research raises the prospect of more effective treatments for cachexia, a profound wasting of fat and muscle occurring in about half of all cancer patients, raising their risk of death, according to scientists from Dana-Farber Cancer Institute.
Many strategies have been tried to reverse the condition, which may cause such frailty that patients can't endure potentially life-saving treatments, but none have had great success.
Scientists reporting in the July 13 advanced online edition of Nature, led by Bruce Spiegelman, PhD, demonstrated that in mice bearing lung tumors, their symptoms of cachexia improved or were prevented when given an antibody that blocked the effects of a protein, PTHrP, secreted by the tumor cells. PTHrP stands for parathyroid hormone-related protein, and is known to be released from many types of cancer cells.
The scientists said their findings are the first to explain in detail how PTHrP from tumors switches on a thermogenic (heat-producing) process in fatty tissues, resulting in unhealthy weight loss.
This tumor-derived protein, they found, stimulated "beige" or brown fat cells mixed with stored white fat in the body, causing the white fat to "brown" that is, generate heat and cause weight loss even when the animals were at rest.
The researchers carried out two experiments using mice that developed lung tumors and cachexia. In one, they administered a polyclonal antibody that specifically neutralizes PTHrP and found that it prevented the wasting almost completely, while untreated animals became mildly cachexic.
In a second experiment, the antibody treatment prevented the loss of muscle mass and improved muscle function, while control animals developed severe muscle-wasting.
"You would have expected, based on our first experiments in cell culture, that blocking PTHrP in the mice would reduce browning of the fat," said Spiegelman. "But we were surprised tha
|Contact: Teresa Herbert|
Dana-Farber Cancer Institute