The Glue of Life

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If living cells didn't have a fondness for sticking together, we would all be colorful gobs of jelly oozing all over the floor. Fortunately, cells hold to a basic biological premise that stickiness is desirable for form and essential for function. They violate this premise at our peril. When cells become either too sticky or too slippery, arteries can get clogged, cancer cells can skate around the body, and inflammation can turn subversive. Researchers have long believed that if they could somehow manipulate stickiness, they would have a formidable new set of tools for healing.

Now, after decades of frustration and obscurity, the world of adhesion science is beginning to fulfill its promise. Researchers who look at many diseases as a failure of stickiness are designing both antisticky drugs and Super Glue-like drugs to treat a range of disorders, including heart disease, transplant rejection, stroke, arthritis, shock and cancer. Michael Gimbrone Jr., head of vascular research at Harvard Medical School, predicts "a whole new generation of therapeutic interventions." Several drugs are now being tried on humans, and early next year the first of them -- a gel that spurs wound healing -- will enter the final U.S. government approval process.

Stickiness is central to almost all biological processes. Cells are able to form organs and function as a unit thanks to a fascinating category of complex glues they secrete known as extracellular matrix. Securing cells in their matrix are Velcro-like patches called cellular-adhesion molecules (CAMs), which are present on every cell except red blood cells. These cellular glues not only hold things together but also play a vital role in growth, fetal development, repair of damaged tissue and elimination of noxious invaders.

But when cellular glues become too sticky or fail to hold, the outcome is often disastrous. In cancer, for instance, advancing tumors often secrete an enzyme that chews up their matrix, freeing malignant cells to leak into the bloodstream. Some inevitably stick and proliferate at sites elsewhere in the body. Thus the lethal process of metastasis may be viewed as a breakdown in stickiness.

At the opposite end of the spectrum are inflammatory diseases like arthritis and multiple sclerosis, in which things have got a bit too sticky. Normally, inflammation is part of the healing process. At a wound site, for example, chemical signals prompt the cells of nearby blood vessels to produce more CAMs, turning the vessels into a kind of biological flypaper that attracts platelets, leukocytes and other repair cells to the scene of destruction. Once healing is under way, the signals subside so the vessels lose their stickiness and inflammation recedes. But in a disease like arthritis, the chemical signal is always present. Vessels remain sticky, and repair cells pile up, causing pain, swelling and other symptoms of chronic inflammation.