Tumor invasion and extracellular matrix degradative enzymes: regulation of activity by organ factors.

Degradation of the extracellular matrix (ECM) during cellular invasion is important to the formation of tumor metastasis. Several types of ECM degradative enzymes have been implicated in metastatic invasion by malignant cells. These enzymes are regulated by various factors which vary qualitatively and quantitatively between organs. Tissue and plasma activators of zymogens, enzyme inhibitors, and cell surface enzyme receptors directly control localized enzyme activities, and the expression of enzymes is modulated by various cytokines, growth factors and ECM components. Thus, the interaction of tumor cells with an organ environment affects the metastatic behavior of the cells. This organ factor regulation is illustrated using human colon carcinoma cells implanted in different organ sites of nude mice. The cells growing in the cecal wall produced high levels of ECM degradative enzymes and metastasized to lymph nodes and liver. In contrast, enzyme production was repressed in colon carcinoma tumors growing in the subcutis and no metastases were formed.