Effect of aprotinin on metastasis of Lewis lung tumor in mice.

Kallikrein activity in human stomach tissue was measured and found to be about threefold higher in cancer tissue than in normal tissue. To clarify the physiological role of this tissue kallikrein, we investigated its effects on the spontaneous metastasis and tumor growth of Lewis tumors (3LL). Antiprotease, aprotinin, and gabexate mesilate (FOY) inhibited spontaneous metastasis but did not inhibit tumor growth, while tissue kallikrein and plasmin enhanced the spontaneous metastasis of 3LL. The results suggest that the inhibitory effects of aprotinin and FOY on metastasis are not only due to an inhibition of tumor cells released by tissue kallikrein, but that tissue kallikrein, a protease, also participates in metastasis. We thus conclude that aprotinin or FOY should be administered either before or immediately after operation to inhibit spontaneous metastasis.