Scientists Spot Factor in Cancer's Spread
A key protein lures malignant cells to bone, study finds
WEDNESDAY, March 29, 2006 (HealthDay News) -- Researchers have identified a molecule that appears to play a critical part in how cancers spread to bones.
Although the experiments were done in mice, the Austrian researchers hope the finding will lead to new treatments that can keep cancers such as breast, prostate and skin cancer from spreading to bone.
They found that a protein in bone called RANKL communicates with a receptor in breast, prostate and skin cancer cells, telling them to migrate.
Fortunately, there's already an available drug designed to block RANKL activity. The researchers are hopeful that the drug might also prevent cancers from spreading to bone.
Their report appears in the March 30 issue of Nature.
"It is actually a very cool story," said lead researcher Dr. Josef Penninger, who began the work while at the University of Toronto, Canada, and now works at the University of Vienna. "Around 120 years ago, it was predicted by an English physician that tissue factors might contribute to the tissue-specific metastases [spread] of cancers."
RANKL is a critical factor in controlling bone turnover and is also a key player in diseases such as osteoporosis, arthritis and tooth loss. In addition, RANKL controls growth of mammary cells to form lactating mammary glands, Penninger said.
"Our new data show that RANKL tells epithelial tumor cells that express the RANKL receptor, called RANK, to move towards the RANKL source," Penninger said. That source, all too often, is bone.
In its study, Penninger's team studied bone metastases in a mouse model of skin cancer. They gave some animals a drug called osteoprotegerin (OPG), known to inhibit RANKL.
The mice treated with OPG had fewer tumors in their bones compared with the untreated mice. In mice treated with OPG, there was significantly less spread of cancer into bones and vertebrae. And, unlike the untreated mice, none of the OPG-treated mice developed paralysis. However, the spread of cancer into other organs was not slowed in mice treated with OPG, the researchers found.
An estimated one million Americans with tumors develop bone metastases every year, and these metastases sometimes trigger massive pain, Penninger said. "If we are correct, one might be able to interfere with metastases, and with this [drug] might allow women with breast cancer, for instance, to have a decent life with less metastases and less cancer pain," he added.
Penninger stressed, however, that these findings are based on mouse studies, which don't always translate to humans. "However, there is already a drug in phase III clinical trials that interferes with RANKL-RANK, and many companies are working on blocking this interaction, which means the idea we generated in mice can be directly tested in humans with cancer in the near future. Time will tell if we are right."
One expert thinks these findings shed light on how cancer cells spread to bone.
"This is an interesting and important paper because it demonstrates the malignant behavior of cancer cells is determined not only by damaged genes that they carry, but in addition, by the environment in which they find themselves," said Robert A. Weinberg, a member of the Whitehead Institute for Biomedical Research and a professor of biology at the Massachusetts Institute of Technology.
The environment is created, in no small part, by signaling proteins that are released by other cell types, Weinberg said. "In the present case, the release of a signaling protein, called RANKL, persuades cancer cells to acquire some of the traits that enable them to metastasize to the organs such as the bone, which indicates that this migration tendency is not inherent in the bone, but rather created by the external environment of the cancer cell," he said.
For more on metastatic cancer, visit the U.S. National Cancer Institute.