Normal cancer cells and Cdc42-deficient cancer cells have also been compared in vivo. When both types of cells were injected into mouse tail veins, control cells spread out more on the vessel endothelium within minutes, suggesting that Cdc42 assists in cell migration. After six weeks, the control cells had generated more metastases than the Cdc42-deficient cells. Invading cancer cells send out protrusions that reach down between neighboring endothelial cells to contact the underlying basement membrane. The cancer cells then spread out on this extracellular matrix so that the endothelial cells retract, and allow the invaders to insert themselves between them. In the absence of Cdc42, cancer cells failed to spread out on the basement membrane, and Cdc42-deficient cells showed reduced adhesion to extracellular matrix-coated coverslips. Cdc42 therefore promotes the attachment of cancer cells to both endothelial cells and the underlying basement membrane during transendothelial migration.