Health Scan: Scientists learn how colon cancer spreads

In colorectal and other cancers, beta-catenin over-accumulates in the cell and inappropriately activates genes, which leads to cancer.

By JUDY SIEGEL-ITZKOVICH
cancer cell 88 (photo credit: )
cancer cell 88
(photo credit: )
Colorectal cancer, which begins as a precancerous polyp and then becomes malignant and aggressive, is one of the most common types of tumor in Western societies. In an article recently published in Cancer Research, Prof. Avri Ben-Ze'ev and Dr. Nancy Gavert of the Weizmann Institute of Science's Molecular Cell Biology Department reveal mechanisms that help this cancer metastasize. In most cases, colorectal cancer is initiated by changes in a key protein - beta-catenin. One of the roles of this protein is to enter the cell nucleus and activate gene expression. But in colorectal and other cancers, beta-catenin over-accumulates in the cell and inappropriately activates genes, which leads to cancer. Surprisingly, one of the genes activated by beta-catenin, which had been previously detected in colorectal cancer cells by Ben-Ze'ev's group, codes for a receptor called L1-CAM. This receptor is a protein usually found on nerve cells, where it plays a role in nerve cell recognition and motility. Ben-Ze'ev wondered what this receptor is doing in cancer cells. His previous research had shown that L1-CAM is expressed only on certain cells located at the invasive front of the tumor tissue, hinting that it could be an important player in metastasis. In this study, the scientists found that colorectal cancer cells engineered to express the L1-CAM gene indeed spread to the liver, while those lacking L1-CAM did not. In collaboration with Prof. Eytan Domany and research student Michal Sheffer of the Rehovot institute's physics of complex systems department, Ben-Ze'ev then compared the expression of genes induced by L1-CAM in cultured colon cancer cells to those in 170 samples of colorectal cancer tissue removed from patients, and in 40 samples of normal colon tissue. Out of some 160 genes induced by L1-CAM, about 60 were highly expressed in the cancerous tissue but not in normal colon tissue. Ben-Ze'ev plans to conduct further research into the role of these genes to uncover L1-CAM's function in metastasis. PREDICT DISEASE RISK ONLINE Some people would prefer not knowing their risk for cancer, diabetes, heart disease, stroke and osteoporosis. For the rest, there is a free Web site called "Your Disease Risk." The Siteman Cancer Center at Washington University's School of Medicine and Barnes-Jewish Hospital in St. Louis recently launched this easy-to-use tool. Located at www.yourdiseaserisk.wustl.edu, the site poses a series of simple questions about medical history, eating habits, exercise and other behaviors and then provides a personalized estimate of risk for 12 different cancers plus heart disease, diabetes, stroke and osteoporosis. Users will also find tips on how to lower their risk, and convenient Web links to fact sheets that describe the origins and symptoms of each disease. They can choose to investigate just one of the diseases, but answers given in one area carry over to all other areas to avoid the need to repeat when learning about more than one disease. "The key message is that we already have information to prevent much of the chronic disease that affects the population," says Prof. Graham Colditz, a disease prevention expert at the center. "If we can spread the word about prevention strategies, people can start early in life to prevent disease later. We know that it can be hard to decide among all the health claims in the media, and we established this site to make it easy for people to find reliable recommendations for better health and to identify strategies that are best for them." It is estimated that healthy lifestyles could prevent over half of cancers, 70 percent of strokes and 80% of heart disease and diabetes. In addition to detailing the impact of well-known factors like smoking, lack of exercise and being overweight, "Your Disease Risk" offers many other important health tips, such as the benefits of calcium and vitamin D for both colon and bone health, the increased risk of diabetes from eating too many refined grains, and the increased risk of stroke in apple-shaped people who carry extra fat around the waist. The site reflects recent evidence from the medical community to assure that it's up to date. "We have a system of review that looks at published scientific research on disease risk and makes additions or changes when significant new data become available," Colditz says. "As we go forward, the prevention and control team at the Siteman Cancer Center will continue to ensure the accuracy and relevance of the site." SYPHILLIS ON THE RISE The Tel Aviv district health office has reported a sharp increase among homosexual men (some with HIV/AIDS) of syphilis infection. This is a phenomenon of the Western world, and it seems they were infected in the West (outside of Israel). The actual number of cases is low, said the Health Ministry, but it worries that this could be the beginning of an outbreak in our region. Syphillis is a bacterial disease passed by vaginal, anal or oral sex, and every sexual encounter with an infected person carries at least a 30% risk of passing it on. The most effective way to prevent transmission is a condom. The symptoms come in three stages: a painless sore on the sexual organ infected, then high fever, a rash on various parts of the body, loss of hair and inflamed lymph glands (when it is most infectious, but this stage passes quickly in a few weeks), and then it infects the brain. It can be easily and cheaply treated with penicillin, but has to be diagnosed early. Since the main symptoms pass quickly, patients think they just had a virus. The presence of the HIV virus along with syphilis makes it more likely that the patient becomes infected with other pathogens as well, and changes the clinical picture so it's harder to diagnose. Once diagnosed, the patient reacts more slowly to antibiotics. In recent years in Western Europe and the US, most of the increase in syphillis has been among homosexuals, many of whom also have HIV/AIDS. Until now in Israel, there has not been such a phenomenon. But the feeling here is that it's just a matter of time before it does break out because of the widespread travel of people between Israel and urban centers in the West. The district health office has prepared an information and counselling campaign on safe sex among homosexuals. People who want to be tested free can go to the Levinsky sexual disease-testing clinic in Tel Aviv (03) 537-3738).