Morphine Fuels Tumors in Mice

Researcher says finding preliminary and not yet applicable to humans

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By
HealthDay Reporter

THURSDAY, Aug. 1, 2002 (HealthDayNews) -- The well-known painkiller morphine may actually stimulate the growth of blood vessels, causing tumors to grow, new research contends.

The animal-study findings, by University of Minnesota Cancer Center researchers, are preliminary and have yet to be proven in humans, and some experts feel they never will be.

"It was a tissue study in mice of a human cell line, and the biology and pharmacology and pharmacodynamics of medication in other species are very different from what can be expected in humans," says Dr. Sean O'Mahony, the medical director of the palliative care service at Montefiore Medical Center in New York City, who adds that he has had cancer patients on morphine for months and years who have experienced no ill effects.

But even if the results are duplicated in other species, the news is not all negative.

"Blood vessel growth can be good and bad," says Kalpna Gupta, lead author of the study, which appears in today's issue of Cancer Research. Stimulating blood vessel growth can actually be beneficial for cardiovascular health and for wound repair, she says.

And even cancer patients, who are often given morphine for pain, need not despair. First of all, morphine is usually not given in early-stage cancer patients. Second of all, the lead author stresses that the results are just too preliminary to draw any firm conclusions.

"This is an animal study in a laboratory and until a human study is done, I really don't think there is any need to agonize," says Gupta, who is an assistant professor in the University of Minnesota Medical School's department of medicine. "One should not get worried with these results; it's purely an experimental study in mice, and we don't know if it will be similar in humans."

In the experiment, doses of morphine proportional to the doses given to human cancer patients caused a human tumor model in mice to grow. The effect did not take place right after the tumor was implanted, but at a later stage of development.

"What happens is the blood vessels do not initiate growth, but they make it grow faster," Gupta explains. "Once the blood vessels have grown to a certain extent, then they take the cells from the tumor and spread them to other parts of the body."

The morphine appeared to work through a particular signaling pathway -- the mitogen-activated protein kinase (MAPK) signaling pathway, which plays a key role in the formation of new blood vessels.

And the morphine also contributed to the survival of endothelial cells, which form blood vessels.

Knowing the mechanism at work here may enable researchers to develop pain-killing compounds that don't have the effect of stimulating blood-vessel growth. Or it may enable researchers to find alternative ways of administering morphine.

Alternatively, the findings, if confirmed, could be used to help with wound healing or cardiovascular medicine.

"We might find a compound to make blood vessels grow faster in wound healing," Gupta says.

"It has a brighter side to it. That's the importance of our basic findings," she adds.

"Blood vessels play a central role in so many diseases, and all these patients receive morphine. So we are working on several aspects so that we can make better use of it when we want its beneficial effects or when we want preventive effects," she says.

What To Do

For more information on the role of angiogenesis in cancer, visit the National Cancer Institute, which also has more on opioids for cancer.

SOURCES: Kalpna Gupta, PhD, assistant professor, hematology, oncology and transplantation division, department of medicine, University of Minnesota Medical School, Minneapolis; Sean O'Mahony, M.D., medical director, palliative care service, Montefiore Medical Center, New York City; Aug. 1, 2002, Cancer Research

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