MOLECULAR ANALYSIS OF CHEMOTAXIS IN METASTATIC CELLS

Significant advances in understanding amoeboid chemotaxis at the molecular level have been made recently using relatively simple model systems that can be manipulated in culture. One of these, Dictyostelium discoideum, has been particularly valuable in analysis of mechanisms involved in agonist regulated pseudopod extension and chemotaxis. Molecular probes and assays developed with this model have been directly applicable to mammalian cell chemotaxis. We propose to dissect, at the molecular level, the signal transduction pathway which regulates pseudopod formation and chemotaxis in Lewis lung carcinoma cells. In these preliminary studies we will apply the Dictyostelium paradigm for this pathway directly to M27 cells using molecular probes and assays already developed for Dictyostelium. We will test the relationship between receptor mediated actin nucleation activity and cell motility events which are involved in several key steps of metastasis. The roles of several candidate proteins in these steps will be evaluated.