Chemokines May Hold Key to Breast Cancer Spread
An extremely important article published in the March 1st issue of the journal Nature has concluded that proteins called chemokines may play a crucial role in the spread (metastasis) of breast cancer from the original tumor to distant sites in the body.
Chemokines are proteins on a cell's surface that normally attract powerful white blood cells called lymphocytes and dendritic cells, which are central to the immune system's ability to recognize and attack foreign invaders such as viruses and infections.
However, according to this new study, certain chemokines also seem to act like "magnets" for attracting breast cancer cells. When these magnet chemokines are present in large numbers on a distant organ, they attract breast cancer cells that have broken away from the original tumor. This may help to explain why some organs eventually become cancerous while others remain cancer-free.
Dr. Albert Zlotnik from DNAX Research Institute in Palo Alto, California and colleagues compared the amounts of chemokine receptors on the surface of normal breast cells to those on breast cancer cells, as well as on the cells of organs to which breast cancer has spread.
In laboratory experiments with mice, they found that breast cancer cells, malignant breast tumors, and tumors at distant sites all expressed extremely high levels of specific chemokine receptors called CXCR4 and CCR7, while normal cells had much lower concentrations of these receptors.
The researchers explained that as the cancer cells break away from the primary tumor and circulate in the body, they are attracted to organs that secrete high levels of these chemokines. Tissues that typically produce high concentrations of the CXCR4 and CCR7 chemokines include lymph nodes, bone marrow, lungs and the liver. This explains why breast cancer tends to spread to these targets, they suggest.
Importantly, the researchers also found that by intercepting these chemokine signals with an antibody, they could significantly reduce the development of tumors in distant sites. For example, breast cancer metastases to the lung were reduced by 60 percent to 80 percent after antibodies against the CXCR4 and CCR7 chemokines were injected into the mice.
The implications of their findings are highly significant, they said. It is conceivable that drugs could soon be tailor-made to specifically inhibit the chemokine signals that encourage breast cancer cells to congregate on distant organs. They further suggest that similar experiments to identify chemokine receptors for other cancers might be just as promising.
In a slightly different way, researchers at the University of California, working with lung cancer cells, found that a different chemokine-secondary lymphoid tissue chemokine or SLC-does not attract cancer cells, but rather appears to super-stimulate the immune system to attack them.
Dr. Steven Dubinett and colleagues, writing in the Journal of Immunology, reported on their experiments with lung cancer cells in laboratory mice. They found that SLC eradicated lung cancer in 40 percent of the mice and dramatically slowed tumor growth in the remaining ones. Laboratory mice not exposed to SLC experienced rapid, unrestricted tumor growth.
Dubinett said their findings will lead to new drugs that will "maximize the cancer-fighting abilities of patients' immune systems," not only with lung cancer, but potentially with a wide range of other cancers and illnesses.
Previous studies have also shown that SLC can inhibit angiogenesis, the process of new blood vessel formation essential to tumor growth. A solid tumor cannot grow and multiply until it creates its own blood supply to obtain necessary oxygen and nutrients.
"The UCLA researchers' discovery that SLC can vigorously stimulate the immune system, combined with existing knowledge about this protein's ability to limit blood vessel formation, makes the protein extremely promising as a basis for new cancer treatments," said Bernard Fox, Ph.D.of Oregon Health Sciences University.
"The work also suggests that SLC could increase the effectiveness of currently available cancer vaccines," he added.
SOURCES:
Nature, March 1, 2001; 410:50-56
Journal of Immunology, May 1, 2000; 164:4558-4563
The American Cancer Society (http://www.cancer.org)
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