Molecular analysis of amoeboid chemotaxis: parallel observations in amoeboid phagocytes and metastatic tumor cells

Abstract

Metastasis is a multistep process in which amoeboid chemotaxis plays a key role in the movement of tumor cells into and out of vessels. On a molecular level, much of what is known about amoeboid chemotaxis has been learned through work with Dictyostelium discoideum, a lower eukaryotic amoeboid phagocyte. One of the first and most crucial events to occur in the actin cytoskeleton following chemotactic stimulation is activation of actin nucleation. This is followed by incorporation of specific actin cross-linking proteins into the cytoskeleton, proteins which are implicated in the extension of pseudopods and filopods. Together, these events have been termed the Cortical Expansion Model for amoeboid chemotaxis. Detailed biochemical analysis has implicated a new actin-capping protein and has shown that one of the cross-linking proteins is Elongation Factor 1a, suggesting a link between chemotaxis and growth control. Preliminary data from parallel studies on neoplastic cells are presented.