The Discovery of Cell Adhesion Molecules

Erkki Ruoslahti, M.D., Ph.D.

Erkki Ruoslahti, M.D., Ph.D. Distinguished Professor, Tumor Microenvironment Director, Vascular Mapping Center

Dr. Erkki Ruoslahti was curious about how cell surface molecules attach cells to their appropriate places in surrounding tissue. He hypothesized that if attachment molecules existed, something must be wrong with them in cancer cells, which lose their attachments and metastasize to distant parts of the body.

While searching for cell attachment molecules, Ruoslahti’s team discovered fibronectin, a protein that forms a scaffold around cells to keep them where they belong. Studying the structure of fibronectin, Dr. Ruoslahti found that cells recognize a small, specific three–amino acid group on the protein, called RGD (Arginine-Glycine-Aspartic Acid). He then showed that the RGD amino acids attracted a family of cell attachment proteins, now known as integrins, and that cell attachment could be controlled with peptides (small chains of amino acids) containing the RGD motif.

A tumor blood vessel after amplified targeting

A tumor blood vessel after amplified targeting

Dr. Ruoslahti’s team found that attachment to fibronectin and related proteins is necessary for cells to stay alive, which is why normal cells cannot leave their home tissue and wander around the body. Malignant cells, however, are resistant to this safety mechanism and can migrate to other sites in the body.

The RGD discovery sparked a world-wide drug development effort that has led to new medicines to treat cancer and prevent arterial narrowing after stent placement. These latter drugs are on the market and several cancer drugs are in clinical trials. The RGD discovery also served as a model to design other integrin inhibitors.

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