Researchers at the Medical College of Wisconsin in Milwaukee have a pending patent on a new synthetic form of a protein involved in certain types of cancers and immune system diseases. The protein, CXCL12, is a chemokine. New information on the structure of the protein was discovered by Brian Volkman, Ph.D., associate professor of biochemistry at the Medical College based on earlier research by Michael Dwinell, Ph.D., associate professor of microbiology and molecular genetics.
It had been previously established that CXCL12 and its target cellular receptor, CXCR4, played an important role in the migration of cancer cells to common sites of tumor formation, such as bone marrow, lymph nodes, liver and lung tissue. Dr. Dwinell’s laboratory established that CXCL12 expression was key to interfering with the progression of cancer.
To discover the new inhibitor, Volkman’s lab created a new three-dimensional model of how the CXCL12 protein interacts with a portion of the CXCR4 receptor. Because previous research on the CXCL12 structure failed to resolve these details, a key step in the spread of metastatic cancer remained poorly understood.
To complete the molecular model for CXCL12 binding to CXCR4, Volkman and Veldkamp discovered that it was necessary to link two CXCL12 molecules, in effect locking it into a form that could not be chemically separated. This locked form of the protein could still bind to the CXCR4 receptor. However, the locked protein displayed different behavior than the unlocked form. A normal CXCL12 protein strongly induces cell migration, but the locked form of the protein caused no cells to migrate at all.
The researchers then ran another experiment to see what would happen if the normal CXCL12 and locked CXCL12 dimer were combined. The combined molecule had the opposite effect of the single molecule, and it resulted in a near elimination of cell migration. This meant they had discovered that it was possible to convert CXCL12 into a protein that inhibits cell migration.
Release Date: September 15, 2008
Source: Medical College of Wisconsin in Milwaukee
