New research published in the journal Gastroenterology reports on the mechanisms of metastatic pancreatic cancer cells, helping to illuminate the reasons why pancreatic cancer spreads. According to the University of Oklahoma College of Medicine scientists who carried out the investigation, the devil is in the details, and the details are dominated by a protein called ZIP4 that is responsible for transporting zinc throughout the body.
Lead researcher on the project Min Li, Ph.D., along with Courtney Houchen, M.D., explains that overexpression of ZIP4 in pancreatic cancer patients triggers tumor cells to change from an epithelial to a mesenchymal phenotype, which allows them to move throughout the body undetected.
"That transition means the tumor cells are doing everything they can to avoid the surveillance of the body's immune system, as well as chemotherapy and other therapies," Li said. "They become more evasive and are able to penetrate the blood vessels, which permits them to go anywhere in the body."
Li explains that during this transition the cancer cells literally change shape, switching from a square shape to a spindle form. They also slow their growth so as to be able to pass by the immune system without detection.
"This is important because when tumors are in the form of epithelial cells, they are easier to kill with chemotherapy," Li said. "But when they switch to mesenchymal cells, they become resistant to treatment. Tumor cells are very smart and are like creatures with multiple faces. That's why we are looking for the right moment to target them with different strategies."
Pancreatic cancer continues to be a challenging cancer to treat. Overall survival rate remains low at 9% and over 60% of patients suffer from metastasis within the first 24 months after surgery. "People diagnosed with many other types of cancers have seen an increased survival rate in the past 30 years, but that's not the case with pancreatic cancer," Li said.
Houchen adds, "Once a patient has metastatic disease, no therapy can extend life more than six to eight months. It's clear that metastatic spread has to be stopped if we're going to improve survival rates. This study helped us to understand the role of ZIP4 in the epithelial-mesenchymal transition. Somewhere in that shape-shifting process is where we need to intervene to stop the metastasis."
Sources: Gastroenterology, Eureka Alert