In vivo imaging of GFP-labeled metastatic tumor cells reveals cell orientat
ion towards blood vessels. Orientation of tumor cells during chemotactic re
sponses to ligands such as EGF begins with lamellipod extension. Evaluation
of some of the downstream events in lamellipod extension indicates: (1) pl
asma membrane distribution other EGF receptor is uniform bur internalized r
eceptor accumulates on the side of the cell closest to the source of EGF; (
2) the alpha p110 isoform of PI-3 kinase is required; ann (3) protrusion of
the lamellipod relies upon the combined actions of the Arp2/3 complex and
cofilin for generation of filamentous actin.