A Tumor's Ticket to Ride

One hallmark of a deadly cancer is its ability to spread like a windblown fire to other parts of the body. Now, scientists have identified an enzyme that may link a tumor's ability to spread with a defect in the self-destruct mechanism built into all cells. The finding, reported in tomorrow's Nature, may help scientists better understand how aggressive cancer cells spawn more tumors.

Normal cells divide only enough to replace others that have aged. But when a decrepit cell ignores the body's commands to self-destruct, it can continue to divide, eventually forming a tumor. But for tumor cells to spread--a process called metastasis--they need several special skills. After leaving the main tumor, the cells must evade the body's defenses and penetrate tissues. Scientists have been searching for the genes and proteins that endow cells with such deadly talents; recently, they have begun to find evidence that some enzymes involved in programmed cell death, or apoptosis, may also enable cancer cells to strike out on their own.

Now, molecular geneticist Adi Kimchi of the Weizmann Institute of Science in Rehovot, Israel, and her colleagues have identified an enzyme, called DAP-kinase, which seems to tighten that link. When DAP-kinase is missing, cells ignore molecular signals that command cells to kill themselves. To better understand how the enzyme is involved in tumor development, Kimchi and her colleagues looked for it in several kinds of lung-cancer cell lines from mice. They noticed an intriguing pattern: the enzyme was missing in aggressive, rapidly spreading cell lines, and present in the tamer ones. When the team inserted the gene for DAP-kinase into aggressive cancer cells and injected them into healthy mice, the cancer did not spread as readily as it did in mice with the enzyme-free cancer cells.

The connection makes sense, Kimchi says, since a breakaway cancer cell ignores a variety of immune system signals that should trigger its death. Her team is now screening tumor samples from patients with several types of cancer--including breast cancer and leukemia--to see if the enzyme is missing. The find, she says, could eventually lead to a gene therapy for particularly pernicious cancers. DAP-kinase, agrees cancer researcher Eric Stanbridge of the University of California, Irvine, might be "one more target to test" for possible gene therapies.

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