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Researchers Find Genetic Link in Bone Cancer

Summary: The discovery of a gene called MET may explain the development of osteosarcoma, a bone cancer found mainly in adolescents, according to a team of Italian scientists. The gene will also provide a target for researchers looking for treatments or a cure for this disease.

Why it's important: Osteosarcoma is a cancer of bone that strikes about 900 people in the US each year. Most of these are adolescents. Although patients are potentially curable with surgery, they need additional treatment with chemotherapy to ensure the best outcome.

What's already known: MET is normally present in all cells and produces a substance called a receptor that helps cells grow. But when MET becomes overactive, it produces too much of the receptor, which leads to too much cell growth. More than 80% of osteosarcomas are found to have excessive activity of the MET gene. Overactivity of MET is also found in kidney cancer, colon cancer, stomach cancer, and others, although not as often.

How this study was done: In the first part of the study the researchers grew normal bone cells, called osteoblasts, in test tube cultures. They then added many copies of the MET gene to the cells. After around 40-60 days, they took away cells that looked cancerous and put them in mice to see whether they would form cancers. Then they tried to reverse these changes by blocking the MET-produced receptor.

What was found: They found that the cells with the extra MET genes started growing more actively. The cells also developed other genetic abnormalities that are typically seen in cancers. Next, the researchers injected the transformed cells into mice. In about 2 months, tumors began to form, indicating that the injected cells were like osteosarcomas. Perhaps the most important part of the test tube experiments happened when the researchers blocked the receptors produced by the MET gene. That was like throwing the process in reverse. Once the receptors were blocked, the cancer cells reverted back to normal.

The bottom line: One of the main problems facing researchers who study genetic changes in cancer cells is which of the many changes is the most important. This study shows that, at least in osteosarcoma, just one change -- overactivity of the MET gene -- can lead to many other genetic changes. This means that just one genetic abnormality in a cell can lead to transformation of that cell into a cancer. Although these experiments dealt only with osteosarcoma, according to the researchers, this situation is likely to be found in other types of cancer as well.

Even more important is the discovery that the genetic abnormalities formed as the cells became cancerous can be reversed by blocking the MET receptors. This means, as the researchers suggested, that this receptor could be a good target for anti-cancer drugs. If drugs can be developed to block this receptor, they might prove to be effective treatments for osteosarcoma and perhaps, other cancers.

Citation: "MET Overexpression Turns Human Primary Osteoblasts Into Osteosarcomas." Published in the May 1, 2006, Cancer Research (Vol. 66, No. 9:4750-4757). First author: Salvatore Patane, Institute for Cancer Research and Treatment, University of Turin School of Medicine, Italy.