Cancer Tumors Clamp Blood Vessels Shut

Anti-cancer drugs can't hit their target when this happens, researchers suggest

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By
HealthDay Reporter

WEDNESDAY, Feb. 18, 2004 (HealthDayNews) -- Scientists have now shown that cancer tumors actually clamp internal blood vessels shut, making it difficult for anti-cancer drugs traveling through those vessels to hit home.

Counteracting this might make it easier for the drugs to get where they need to go, but it also might open up another avenue for cancer cells to spread, the researchers warn.

Drug delivery can indeed be a problem in some cancer patients, says Dr. Jay Brooks, chief of hematology/oncology at the Ochsner Clinic Foundation in New Orleans. Lack of adequate blood flow can also be a big issue for radiation therapy, which requires oxygen to get to the tumor, he adds.

"For many years, we've realized that tumors have areas where there are dead cells or blood cells don't adequately feed the centers," says Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society in Atlanta. "We've been trying to find out what we can do to improve oxygenation and therapy directed at cancers by trying to overcome these areas of low oxygen that are present in cancers. It seems intuitive, but this is an actual laboratory demonstration."

The demonstration was done with mice, however, which means that much more research needs to be done before scientists can begin to know what the implications are for humans.

Rakesh K. Jain, director of the Steele Laboratory at Massachusetts General Hospital and the lead author of a brief communication on the discovery in the Feb. 19 issue of Nature, likens the process to a garden hose lying on the driveway.

If you drive the wheels of the car on top of the hose, the water flow will stop. "That's exactly what cancer cells do to vessels," he says. "They compress many of the blood vessels by proliferating around them."

While Jain, who is also a professor of tumor biology at Harvard Medical School, and his colleagues had long suspected this might be the case, they lacked a way to prove it. They needed a drug that would kill only cancer cells and not blood vessel cells.

"If I could kill cancer cells around the blood vessels, then the vessels should open up," Jain says.

Eventually, the researchers decided to graft human cancer cells into mice, then treat them with diphtheria toxin, a drug that kills human cells while sparing mouse cells.

As expected, the tumor cells started to die off and the blood vessels started to open up and become functional again.

But something unexpected also happened (or didn't happen). "The surprise came with the lymphatic vessels," Jain says.

The job of the lymphatic vessels is to drain fluid from organs and tumors. In this model, the lymphatic vessels opened up, but they didn't start functioning again.

"Apparently, the tumor is somehow irreversibly damaging lymphatic vessels so they are unable to function," Jain says. "We do not yet know how this is happening."

There is another unanswered question: Will restoring blood flow also allow cancer cells to escape and migrate to other parts of the body? "It might also be able to carry cancer cells out and contribute to metastasis," Jain says. "We don't know that yet. That's a worry."

The study itself is quite preliminary, and not all tumors behave the same way.

"This is a very experimental setting, but there's a whole biology of relationships between blood vessels and lymphatic control with tumors that we're going to be studying and hopefully exploiting," Brooks says.

More information

The National Cancer Institute has more on cancer metastasis. The American Cancer Society has information on bone metastasis.

SOURCES: Rakesh K. Jain, Ph.D., professor, tumor biology, Harvard Medical School, and director, Steele Laboratory, Massachusetts General Hospital, Boston; Len Lichtenfeld, M.D., deputy chief medical officer, American Cancer Society, Atlanta; Jay Brooks, M.D., chief, hematology/oncology, Ochsner Clinic Foundation, New Orleans; Feb. 19, 2004, Nature

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