Successful tumors supply themselves with a steady source of blood by triggering the growth of new vessels. On page 691, Beauvais et al. find a new way to disrupt that process.

Metastatic tumors up-regulate the integrins αvβ3 and αvβ5, which prompt endothelial cells to multiply, migrate, and thus lay down new vessel branches. Integrin activation requires a connection between the integrin and the cell matrix, which is provided by the matrix receptor syndecan-1. In past studies, these authors showed that syndecan-1 was necessary for integrin activation in breast cancer cells in vitro.

Pharmacological integrin inhibitors have recently been developed and are being tested for their efficacy as tumor-stopping agents. But blocking syndecan-1 may be even more effective, suggest Beauvais et al. Here, the authors blocked the integrin–syndecan–matrix interaction with a peptide (“synstatin”) derived from syndecan's site of integrin engagement.

When synstatin is present, syndecan-integrin clusters cannot form, and integrin activation is blunted. Synstatin blocked integrin activation on vascular endothelial cells in vitro, the authors found. And injecting synstatin into mice slowed tumor growth and new vessel formation. Synstatin also impeded vessel growth in a mouse model of corneal angiogenesis.

By preventing integrins from engaging the matrix, the authors expect a more thorough block of integrin signaling than can be achieved with other kinds of inhibitors. Although some pharmacological peptides are rapidly cleared from circulation before they can act, synstatin's long-lasting effects in mice suggests that this may not be a problem.