2003 年 11 巻 2 号 p. 75-83
To explore the proteolysis of extracellular matrix by the invasion of growing tumor cells, a metastatic pharyngeal carcinoma cell line (Detroit 562) was cultured in Type-I collagen gel, and enzymatic and confocal laser-scanning microscopic (CLSM) analyses were carried out. Cells grew exponentially and degraded the collagen matrix. Concomitant with this growth were increased expressions of both urokinase-type plasminogen activator and matrix metalloproteinases (MMPs), which were the major proteolytic enzymes involved in the hydrolysis of the matrix. MMPs were identified as the 72-kDa and the 92-kDa species. CLSM demonstrated that colonies formed holes (micro-voids) and connecting tunnels around their peripheries. These findings and direct visualization suggest extensive proteolysis of pericellular matrix by the activated MMPs, providing an in vitro model for the invasive spread of tumor cells.