Mutations that activate Notch have been identified in several cancers. Weiland et al. find that Notch1 signaling within endothelial cells (ECs) promotes the invasion of distant organs by tumors. Abnormally high levels of active Notch1 are found in blood vessels associated with advanced human cancers. Similarly, in mice, when Notch1 is activated in the ECs, circulating tumor cells increase in the bloodstream. Mobilization of tumor cells leads to the recruitment of white blood cells called neutrophils into the tumors and the production of VCAM1, which is used by cancer cells to adhere to new sites. Therapies in mice targeting either VCAM1 or Notch1 are effective in reducing neutrophil influx and tumor progression.
