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.