The study will be published in the Jan. 14 edition of the Journal of Biological Chemistry.
Pizzo credits lead author and signaling pathway expert, biochemist Uma Misra, Ph.D., with deducing that PSA may be involved in a signaling feedback loop that promotes more aggressive behavior in the human prostate cancer cells.
"If you were a cancer cell, you would like to turn on cell growth, turn off the process of death by cell apoptosis and you'd like to be able to migrate, and when the α2M antibody binds with the protease PSA molecule, all of that happens," Pizzo said.
Years ago, Misra discovered the GRP78 receptor on the prostate tumor cell surface, the receptor that binds the α2M antibody and the α2M-PSA complex.
"We were surprised to find that this complex binds with the protein GRP78, because we thought the GRP78 molecule only lived deep inside the cell, where it was busy taking improperly folded proteins and helping them to fold properly," Pizzo said. "It was a surprise to find GRP78 on the cell surface, with other functions. Based on the dogma of the time, we didn't think that GRP78 could function as a receptor. Even when we identified it, I doubted our findings."
Pizzo said that since Misra first made the observation about GRP78 working as a receptor, "it has turned into a cottage industry. GRP78 receptors have been discovered on many other cancer cells, including breast, ovary, liver, colon, melanoma and lung cancer cells."
"This is going to be a generic phenomenon to tumors," predicted Pizzo, who is also working to learn more about this receptor in other types of cancer cells. "Not all tumors will express GRP78 on their cell surfaces, but when they do, it probably will be a harbinger of a bad outcome."
"I think we will find that nature favors conservation and it makes sense that the body uses the
|Contact: Mary Jane Gore|
Duke University Medical Center