The production of collagenase, protease, leucine aminopeptidase, and prostaglandin E2 by rat tumor increased with the growth of tumor. The syntheses of collagenase, protease, and leucine aminopeptidase were significantly inhibited by indomethacin. Inhibition of collagenase, protease, and leucine aminopeptidase syntheses was overcome by the addition of prostaglandin E2 at a concentration equivalent to the endogeneous level of prostaglandin E2 in rat tumor. These findings suggested that prostaglandin E2, possibly derived from tumor cells, was involved in stimulating the tumor connective tissue stroma to produce collagenase, protease, and leucine aminopeptidase, which promoted tumor cell invasion.
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