The ability of some breast cancers to grow rapidly and tenaciously may be the result of a survival strategy borrowed from brain cells, scientists at Dana-Farber Cancer Institute have found.
In a study to be published in the Sept. 16 issue of the Proceedings of the National Academy of Science, investigators led by Kornelia Polyak, MD, PhD, report that a protein known to enhance the survival of certain brain cells is present in about 10 percent of invasive breast tumors. The protein, called dermcidin, or DCD, was also found to contribute to cachexia, a muscle-wasting and weight-losing condition that afflicts many cancer patients.
"The fact that DCD protects nerve cells in the brain from damage suggests it may have a similar effect on certain breast cancer cells – by enabling them to grow faster and avoid apoptosis [the natural process that causes cells to die after a set number of divisions]," says Polyak, the study's senior author. "It appears that the same substance that is beneficial in the case of nerve cells can play a harmful role in the development of certain breast cancers."
The discovery of DCD's effect on different types of cells may lead to new ways of treating not only breast cancer but also conditions such as stroke and Alzheimer's disease, which involve the death of large numbers of brain cells.
Polyak and her colleagues decided to focus on DCD after finding it to be especially prevalent in invasive breast cancer cells. Using sophisticated gene-screening techniques, they tested 600 breast tumor samples and determined that although normal breast cells do not contain the protein, it is overabundant in about 10 percent of all invasive breast cancers.
A British research team had previously discovered that only two other types of cells in the body normally produce DCD: nerve cells of the brain and cells of the sweat glands. In both cases, the protein improves the cells' chances of survival by shielding them from damage and accelerating their growth.
With this as a clue, Polyak and her colleagues determined that the protein provides the same service to cells in invasive breast cancers. "We found that when DCD is produced in large amounts, breast tumors tend to be larger and more likely to spread beyond the breast," remarks Polyak, who is also an assistant professor of medicine at Harvard Medical School. "The protein was expressed at these high levels only in invasive tumors, not in early-stage ones."
At the same time, the investigators found that DCD apparently contributes to cachexia. A disorder in which muscle and fat cells essentially digest themselves, leading to a wasting-away of the body, cachexia is one of cancer's most notorious hallmarks. While the precise nature of DCD's involvement in cachexia isn't known, it's clear that the protein has a very different effect on muscle cells than on nerve cells.
The response to DCD, whether in nerve cells or invasive breast cancer cells, is triggered when a chemical signal docks at "receptors" on the cells' surface. Polyak and her associates are currently exploring ways of influencing those receptors. Blocking them in invasive breast cancers may slow the tumors' growth, while stimulating them in patients with stroke or Alzheimer's disease may protect nerve cells from dying.
"DCD's role in a variety of different disorders makes it an attractive target for new therapies," Polyak remarks. "Increasing or decreasing its production in certain sets of cells may offer a promising approach to treatment."
Co-authors of the study are based at Brigham and Women's Hospital, Harvard Medical School, Harvard School of Public Health, the Comprehensive Cancer Center at the University of California, San Francisco, John Hopkins University, Duke University Medical Center, and the Ardais Corp. of Lexington, Mass.
The study was funded in part by the National Cancer Institute and the National Institute on Aging.
Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.
Dale Porter, Stanislawa Weremowicz, Koei Chin, Pankaj Seth, Aparna Keshaviah, Jaana Lahti-Domenici, Young Kyung Bae, Constance L. Monitto, Ana Merlos-Suarez, Jennifer Chan, Christine M. Hulette, Andrea Richardson, Cynthia C. Morton, Jeffrey Marks, Mabel Duyao, Ralph Hruban, Edward Gabrielson, Rebecca Gelman, and Kornelia Polyak
A neural survival factor is a candidate oncogene in breast cancer
PNAS published September 2, 2003
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