Scientists Identify Protein That may Stop Cancer Spread

by Rajashri on Sep 16 2008 4:13 PM

A new synthetic form of protein that may stop cancer progression has been identified by researchers from Medical College of Wisconsin in Milwaukee.

The protein CXCL12, also known as a chemokine, regulates the movement of cells into tissues and recruit infection-fighting white blood cells to infected and injured sites. They essentially act as homing beacons for the immune system.

"We hope that stable synthetic versions of CXCL12 will allow us to conduct proof-of-concept studies about cancer prevention," said Brian Volkman, Ph.D., associate professor of biochemistry at the Medical College.

"It's clear that CXCL12 is an important molecule for designing new ways to treat cancer," he added.

Previous studies have shown that CXCL12 and its target cellular receptor, CXCR4, played an important role in the migration of cancer cells to common sites of tumour formation, such as bone marrow, lymph nodes, liver and lung tissue.

During the study, the researchers created a new three-dimensional model of how the CXCL12 protein interacts with a portion of the CXCR4 receptor.

To complete the molecular model for CXCL12 binding to CXCR4, the researchers 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, known as a dimer, could still bind to the CXCR4 receptor.

However, the locked protein displayed different behaviour 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.

"This was exciting because it was genuinely unexpected," said Dr. Volkman.

"It was the strongest suggestion yet that chemokine dimers might really be active participants in directing the migration of white blood cells and possibly other kinds of cells," he added.

The findings are published in the September issue of Science Signalling, a new online journal published by Science magazine.