A new view of cancer  pg. 5

Rolling along—a nefarious journey
According to one model, macrophages roll along the lining of blood vessels, “tracking the scent” of chemical messengers called chemokines released by tumor cells. Once at the tumor site, they are “re-educated” by the tumor to produce factors that help it grow and spread.
Guided by factors in their “micro-environment,” some tumor cells find their way to a blood vessel. Once in the bloodstream, a chemokine trail—or possibly a blood cell “chaperone”—leads them to another tissue. This process is known as metastasis.
Illustrations by Dominic Doyle
An example of this cellular “cross-talk” is the tissue remodeling that occurs during development or wound healing with the help of the matrix metalloproteinases (MMPs), a family of enzymes involved in a wide range of physiological processes. “Not only do they degrade the matrix, they release biologically active factors that are involved in calling in inflammatory cells and in angiogenesis,” says Lynn Matrisian, Ph.D., chair of Cancer Biology at Vanderbilt who, as a post-doctoral fellow, cloned the first full-length MMP in the mid-1980s.

MMPs also are believed to contribute to metastasis, the major cause of death from cancer, by helping to increase the tumor’s blood supply and means of escape to other parts of the body. The first synthetic MMP inhibitor was tested in humans in 1992, but by 2002, several clinical trials had failed to show any survival benefit.

That’s not surprising, says Matrisian, past president of the American Association of Cancer Research. MMP inhibitors “don’t stop cancer in its tracks,” she says. “What we learned is they change the rate of progression (of the disease).”

In 2002, Matrisian, Coussens and their Vanderbilt colleague Barbara Fingleton, Ph.D., predicted in an article in Science magazine that MMP inhibition would help prolong survival to the point that patients died of “old age” before they died of cancer. “But you can’t give it at the ninth hour,” Matrisian says. “You have to give it earlier, or you have to give it in combination (with other drugs)… or you have to think about prevention.”

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