Cell Motility in Tumor Invasion.

摘要

Our overall objective is to understand how dysregulation of cell migration contributes to tumor cell invasiveness in prostate cancer. A combination of correlative epidemiological studies and basic experimental investigations demonstrate a role for upregulated EGF receptor (EGFR) signaling of motility in tumor progression. EGFR-mediated cell motility has been demonstrated to be critical for tumor invasion. Our central premise is that prostate tumor cell invasiveness can be inhibited by interfering with the specific motility-associated calpain activation that governs the critical underlying biophysical process of de-adhesion. Prior work has shown that integrin/matrix binding and growth factor stimulation jointly regulate cell locomotion. These studies have identified cell/substratum adhesiveness, especially the ability of a cell to detach at its trailing edge, as a primary governor of cell locomotion. We have recently found that this tail detachment is regulated by calpain activation. We are employing a set of model prostate tumor cell lines including a panel of syngeneic androgen-independent DU-145 cells that vary in invasiveness. Our findings in the first year showed that disruption of calpain activation and de-adhesion can block tumor invasiveness in vitro. This has been extended in the second year to demonstrate that this also applies in animal models of tumor invasiveness.