Kalpna Gupta, Ph.D., assistant professor in the hematology, oncology and transplantation division of the uUniversity's department of medicine and lead author of the study, found that doses of morphine similar to doses given to cancer patients activate the mitogen-activated protein kinase (MAPK) signaling pathway in human endothelial cells (cells that form blood vessels). MAPK plays a key role in promoting endothelial cell multiplication and angiogenesis (formation of new blood vessels). Angiogenesis can cause tumor growth by providing nutrients to growing tumors and by transporting cancer cells from a tumor to other parts of the body. Gupta notes that morphine did not promote initial or early growth of tumors in this study.
The researchers also found that morphine promotes endothelial cell survival by activating Akt, the key survival-signaling pathway inside these cells. Endothelial cell survival is crucial to the process of angiogenesis. This study demonstrates for the first time that morphine-induced effects on blood vessel cells can lead to angiogenesis-dependent tumor growth in mice.
"Despite the widespread use of morphine to treat pain in many medical conditions like cancer, little was known about how this drug affects blood vessels or cancer," says Gupta. "Our study shows that morphine stimulates the formation of new blood vessels inside the tumor, which in turn allows increased growth of tumors in mice." Gupta cautions that there is currently no scientific data that indicates morphine or similar pain medications will lead to increased growth of cancers in humans.
According to Gupta, these findings could lead to the development of new treatments to manage cancer pain. For example, understanding the activity of opioids like morphine in angiogenesis may lead to new drugs that selectively relieve pain without stimulating angiogenesis. The researchers said that their findings call for further investigation of the role of morphine and similar opioid drugs in tumor growth in patients.
Co-authors of the study include university colleagues Smita Kshirsagar, Ph.D.; Liming Chang, Ph.D.; Robert Schwartz; Ping-Y. Law, Ph.D.; Doug Yee, M.D.; and Robert P. Hebbel, M.D.
The University of Minnesota Cancer Center is a National Cancer Institute-designated Comprehensive Cancer Center. Awarded more than $68 million in peer-reviewed grants during fiscal year 2001, the center conducts cancer research that advances knowledge and enhances care. The center also engages in community outreach and public education efforts addressing cancer. For more information on cancer in general, visit the Web site at www.cancer.umn.edu or call 1-888-CANCER MN (1-888-226-2376 or 612-624-2620).
Kalpna Gupta, Ph. D., assistant professor (contact through Brenda Hudson or Amy Leslie)
Brenda Hudson, Academic Health Center, (612) 624-5680
Amy Leslie, Cancer Center, (612) 626-0410
Journal
Cancer Research