Cancer, A Wound That Doesn't Heal
Wound healing and cancer progression have striking similarities, including the growth of new blood vessels (angiogenesis), the rearrangement of the molecular matrix around the cells, and changes in how cells attach to each other.
Comment: This is an interesting and important concept. The genetic programs activated within cells in the healing of a wound may also contribute to the ability of tumor cells for invasion and metastasis (spread).
WOUND-HEALING GENES INFLUENCE CANCER PROGRESSION, SAY STANFORD RESEARCHERS
STANFORD, Calif.-- Genes that help wounds heal are most often the "good guys," but a new study paints them as the enemy in some types of cancer. Researchers at the Stanford University School of Medicine have found that some tumors activate these wound-healing genes and, when they do, the tumors are more likely to spread. This work could help highlight new ways to treat the disease along with helping doctors decide which cancers to approach more aggressively.
"This is a feature we can find early on in the disease and it could change the way cancer is treated," said Howard Chang, MD, PhD, a postdoctoral scholar and lead author of the paper. The work appears in the Jan. 19 edition of Public Library of Science Biology.
The research group, led by Patrick Brown, MD, PhD, professor of biochemistry, took an unusual approach in finding the telltale genes. In most studies, scientists analyze tumor samples and look for genes that are more active compared to normal tissue. Such studies have produced long lists of genes involved in cancer biology but don't provide clues about what role those genes may be playing.
Chang started from the opposite direction. He knew wound healing and cancer progression had some similarities, including the growth of new blood vessels, rearrangement of the molecular matrix around the cells and changes in how cells attach to each other. "Wound healing is a process that allows cells to break normal constraints on their growth and cross boundaries. If a cell can access that program, that's a good environment for cancer," Chang said.
The researchers started by finding which genes are active in cells exposed to clotted blood as a model of cells in the wound-healing process. Then Chang and his colleagues looked to see whether those same genes were active in tumor samples.
The researchers found that prostate and liver cancers always activated wound-healing genes, while tumors in the breast, colon and prostate were mixed. In these variable tissues, tumors with active wound-healing genes turned out to be highly aggressive and were more likely to spread to other tissues.
Chang said assessing wound-healing genes could help doctors choose the best treatment for a patient. "There are a lot of drugs that work only on certain type of cancers. If you realize that different drugs work on a specific abnormality, doctors can match the drug to the problem," he said.
The best-known example of such pharmaceutical matchmaking is the drug Herceptin, which specifically treats breast cancers with an active version of the gene Her2/Neu.
Most doctors don't have the ability to screen tumor samples for active genes, but they routinely test for the presence of proteins made by genes, as with Her2/Neu. Julie Sneddon, a biochemistry graduate student and second author on the paper, has been working on a similar test to identify tumors that churn out wound-healing proteins.
Chang said the next step is learning how best to treat tumors that produce these proteins. Because wound healing is a well-understood process, researchers may be able to disrupt the process and slow the cancer's spread. "There are drugs coming out that block blood vessel growth, so perhaps those drugs should be targeted to this population of patients," Chang said.
Additional Stanford researchers who contributed to this work include postdoctoral scholars Ruchira Sood, PhD, and Jen-Tsan Chi, MD, PhD; Ash Alizadeh, MD, PhD, a former graduate student; Rob West, MD, PhD, clinical instructor of pathology; Kelli Montgomery, research associate; and Matt van de Rijn, MD, PhD, associate professor of pathology.
Source: Stanford School of Medicine News Release, January 12, 2004 (http://mednews.stanford.edu/releases/2004)
Last Editorial Review: 7/7/2004