Molecular Mechanisms for Invasion and Metastasis of Tumor Cells and Effects of Food Factors

Young Investigator Award of the 2004's JSNFS

Abstract

Tumor cells are known to display two critical biological characteristics: endless proliferation; and metastasis. Metastasis represents a complex and sequential cascade of events leading to the dissemination of tumor cells to distant sites. In many cases, metastasis may prove lethal in the course of clinical treatment. Invasion comprises the most important and characteristic event in tumor metastasis, and inhibition of invasion is thought to lead to inhibition of metastasis. To identify food factors displaying anti-invasive. activity, we have established a novel screening system by co-culturing rat ascites hepatoma cell line of AH109A with mesentery-derived mesothelial cells. We also investigated the bioavailability of screened food factors by determining the effectiveness of sera from rats orally administered those food factors. Food factors such as teas and coffee demonstrated suppressive effects on tumor cell proliferation and metastasis in hepatoma-bearing rats. In the course of the study, we found that anti-oxidative activities were important for anti-invasive activities. Reactive oxygen species (ROS) are known to be profoundly involved in tumor invasion. We found that ROS stimulate the autocrine loop of HGF-c-met in the invasion process of rat hepatoma cells, and anti-oxidative food factors suppress tumor cell invasion by shutting down this loop.