Scientists ID Defective Cell Extrusion Mechanism by Which Pancreatic Cancer May Begin; Same Defect May Also Be Involved in Lung Cancer and Colon Cancer; Work Suggests Possible Effectiveness of FAK Inhibitors

Researchers at the Huntsman Cancer Institute (HCI) at the University of Utah, and at collaborating institutions, have found that defects in how cells are squeezed out of overcrowded tissue to die, a process called extrusion, may be a mechanism by which pancreatic cancer begins. From these findings, the scientists may have identified an effective way to reverse the defective extrusion's effects without destroying normal tissues nearby. The results were published online on January 26, 2015 in an open-access article in the journal eLife. The study focuses on the epithelia, tissues lining the cavities and surfaces of structures throughout the body, including organs such as the pancreas. It is already well-established that most solid tumors arise from this type of tissue. The HCI research team analyzed previous published microarray data and found that a receptor for the lipid sphingosine 1-phosphate (S1P2) that is critical for the extrusion process is significantly reduced in the most common type of pancreas cancer known as pancreatic ductal adenocarcinoma (PDAC), lung cancer, and some types of colon cancer--all aggressive cancers that resist treatment with chemotherapy. Focusing on cells from PDAC tumors, the team found that reduced S1P2 levels led to reduced extrusion and cell death rates. About 50% of the cells did not extrude and formed masses, while most of the remaining ones extruded underneath instead of outside the cell layer. "This kind of altered extrusion may be a common hallmark of invasive tumor types," said Jody Rosenblatt, Ph.D., co-author of the study, Associate Professor in the Department of Oncological Sciences at the University of Utah School of Medicine, and an HCI investigator.
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