The researchers are hopeful that the discovery will lead to new, less-toxic drug therapies for the disease. Their strategy hinges on "knocking out" the cancer-spreading gene in order to halt the movement of cancer cells from the primary tumor site.
"We've found a gene that is essential for the migration of cells. And potentially, by blocking the action of this gene product, we can control the cancer and manage the disease," says lead author Dr. Richard Pestell, who is now chairman of Georgetown's department of oncology. The work was done at the Albert Einstein College of Medicine, before Pestell went to Georgetown. It will appear in the May issue of Molecular Biology of the Cell.
Pestell's team was tipped off that the cyclin D1 gene might play a role in metastasis after learning that patients with spreading cancer also had an over-expression of the gene.
The scientists tested this curious phenomenon in the laboratory by examining the progression of cancer in mice that were missing the cyclin D1 gene. Using a high-powered microscope, they observed that the cancer cells were missing an outer "ruffle" layer that would typically enable them to migrate. Without this structure, the cancerous cells were immobilized and the disease was held in check.
Current therapies for cancer halt the disease's spread by hobbling the cell division process. As a result, patients suffer from hair loss and other side effects. If the researchers can determine exactly how cell migration differs from cell proliferation, new therapies could focus on just the cells that migrate, which would eliminate many of the debilitating symptoms that come with chemotherapy.
While suggestive, the findings are not conclusive, says Dr. Danny Welch, a professor of pathology at University of Alabama-Birmingham.
"The data show that mice without the cyclin D1gene ... tend to develop tumors at a much lower rate. And if you couple those observations with the clinical observation that cyclin D1 is associated with more aggressive tumor spread, the implication is that it may control metastasis," he says.
"But they haven't tested that theory directly in this paper. It's a great lead-in for a big number of future experiments," he adds.
While such a treatment would not eliminate a cancerous tumor, it would control the disease and prevent the cancer from attacking other parts of the body, Pestell says.
"Like diabetes, patients could live normally with the cancer in place," he adds.