A. Ben-Ze'ev and N. Gavert/Weizmann Institute of Science

Edgy and nervy.
L1CAM protein (brown in top panel) resides in cells poised to break from the cancer's bulk (cells with b-catenin are brown in bottom panel) and invade other tissues.

Nasty Cancers Have Some Nerve

SAN FRANCISCO, CALIFORNIA--Some cancers keep to themselves as compact tumors while others aren't content until they've spread through the body. What makes one more aggressive than the other? One explanation, according to new research, is the presence of a protein normally found in neurons. Experts say the work may offer a new target in the fight against colon and other types of cancers.

As cells become cancerous, they produce more of a protein called b-catenin. The protein acts like a molecular switch, turning specific genes on and off. Reasoning that b-catenin might turn on other genes that help cancers along, such as those that make them spread, cancer biologists Avri Ben-Ze'ev and Nancy Gavert of the Weizman Institute of Science in Israel and colleagues set about looking for such genes.

Colleagues of Ben-Ze'ev had examined the effect of turning off b-catenin on other, unrelated functions within cells. In the current study, they scanned some of the genes involved in these processes and found a gene called L1CAM, whose protein is well-known to wire nerve cells together. To determine whether L1CAM has a role in cancer, the researchers looked for its protein in normal skin cells, cultured noncancerous cells, and aggressive melanomas from 11 patients. While the normal cells contained no L1CAM protein, the cancers harbored quite a lot. When the team blocked the activity of L1CAM in cultured human colon cancer cells, the cells' growth slowed dramatically.

L1CAM's role in cancer appears to be to make the disease more aggressive. When the team turned the gene on in a set of colon cancer cells and injected them into mouse spleens, the cells spread into the animals' livers; cells that didn't make the L1CAM protein stayed put. The protein seems to help cancers spread in people too: 50% of colon cancer patients with high amounts of L1CAM protein in their tumors had the cancer spread within 5 years of treatment, compared to only 14% of individuals with low amounts, the researchers reported here 13 December at a meeting of the American Society for Cell Biology.

L1CAM could turn out to be a prognostic factor for cancer development and a potential target for therapy, says cancer biologist Michael Shtutman of the Ordway Research Institute in Albany, New York. In addition, it could be a useful tool to help researchers understand how cancers invade tissues and metastasize, he says.

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