When mice with ovarian cancer are stressed, their tumors grow and spread more quickly, but that effect can be blocked using a medication commonly prescribed for heart disease, according to a preclinical study by researchers at The University of Texas M. D. Anderson Cancer Center.
The finding, published in the journal Nature Medicine, now available on-line, provides the first measurable link between psychological stress and the biological processes that make ovarian tumors grow and spread. Specifically, the researchers showed that stress hormones bind to receptors directly on tumor cells and, in turn, stimulate new blood vessel growth and other factors that lead to faster and more aggressive tumors.
"This study provides a new understanding of how chronic stress and stress factors drive tumor growth," says Anil Sood, M.D., associate professor of gynecologic oncology and cancer biology and director of ovarian cancer research.
In fact, when the researchers blocked the stress hormone receptors in their experimental system using a heart disease drug called propranolol, also known as a "beta blocker," they were able to stop the negative effects of stress on tumor growth. The researchers used the beta blocker because the same hormone receptors, called beta adrenergic receptors, are found in the heart and normally work to maintain blood flow.
"The concept of stress hormone receptors directly driving cancer growth is very new," says Sood, the study's senior author. "Not much had been known about how often these receptors are expressed in cancer, and more importantly, whether they had any functional significance. Our research opens a new area of investigation."
The research began when Sood and his colleague Susan Lutgendorf found an association between ovarian cancer patients who reported high levels of stress in their lives and an increase in a factor that stimulates blood vessel growth in tumors. By contrast, patients who had more social support in their lives had lower levels of this factor. Sood wondered if hormones associated with chronic stress might affect how cancers grow.
Sood's research team, led by investigators Premal Thaker, M.D., Liz Han, M.D., and Aparna Kamat, M.D., in the Department of Gynecologic Oncology, developed a mouse model of ovarian cancer to study the link. In their experiments, the researchers confined the mice in a small space for zero, two or six hours during the day.
The confinement caused the mice to produce the same stress hormones as humans produce when they are under stress. These beta adrenergic hormones are sometimes called the "fight-or-flight" hormones because they are released when people are fearful or threatened, and are also responsible for causing the heart to beat harder and faster.