Cancer Cocoon

Do tumors have a shield?

One of cancer's great puzzles is how malignancies escape detection and destruction by the body's protective immune system. Cancer cells are known to carry distinctive surface proteins that should act as antigens, immunological alarms. Normally, the bodily defenses respond by alerting and marshaling antibodies, lymphocytes and macrophages, which attack the unwanted cells. But in the case of cancer, the attack is stifled or never gets under way.

Last week a husband-wife team at Boston's Massachusetts General Hospital and their colleagues offered a possible explanation that may also suggest new cancer therapies. In their view, some malignant cells escape detection by getting the body to form a womblike cocoon around the tumor.

The discovery by Pathologists Harold and Ann Dvorak, along with W. Hallowell Churchill of Boston's Peter Bent Brigham Hospital, results from three years of work with guinea pigs. It is based on two vital clues provided by earlier investigators: first, some tumors have nearby deposits of fibrin, the substance of blood clots, which prevents further bleeding after injury; second, tumors are often associated with slight, local hemorrhaging. Using sophisticated microscopy techniques, the Boston researchers began looking at the point where the tumor meets healthy tissue. Explains Harold Dvorak: "That would have to be the battlefield on which they fought."

What the team found was that early in their development, tumors secrete three powerful chemicals that promote formation of a protective shield of fibrin gel around them. One substance encourages nearby blood vessels to leak plasma; another turns fibrinogen, a plasma constitutent, into fibrin; the third diverts immune cells away from the growing shield. Dvorak speculates that the tumor's chemical weaponry is so sophisticated that the fibrin itself encourages growth of blood vessels in the vicinity of the tumor, providing the malignant cells with a nourishing blood supply. As it enlarges, the tumor appears to secrete a fourth chemical that dissolves the shell from the inside yet does not break its outer layer.

By all this biochemical wizardry, the tumor has in effect duped the body into regarding it as a wound to be healed rather than as a lethal intruder. Says Dvorak: "The tumor is a sophisticated and subtle parasite that uses the host's own defense mechanism against the host."

The new theory is still far from proved, but it could have important consequences. If human tumors turn out to work in the same way, more effective strategies against cancer could be developed. One possibility is already being tried by specialists: administering anti-clotting drugs to prevent fibrin deposits.

Another approach would be to find a substance that breaks down the cocoon from the outside, allowing the immune cells to get at the tumor. A third tactic that Dvorak and his colleagues are planning to explore is the production of antibodies against the tumor's own chemicals.

There is one caveat in these strategies: all could possibly interfere with healing processes in normal tissue and lead to serious bleeding. But, says Dvorak, some bleeding might be less dangerous than many of the destructive anticancer drugs and radiation treatments now being used.

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