Participation of macrophages in the mechanism mediating the enhancement of metastasis formation after tumour resection.

Abstract

The number of spontaneous lung metastases and the frequency of metastasis formation in the lymph nodes of mice were studied following the induction of tumour growth by injection of tumour cells. A syngeneic transplantable mammary adenocarcinoma, MMT 1, from C3H/He mice, and a cloned strain, MMTV4, obtained by treating MMT1 cells with 5-azacytidine in vitro, were used. No differences between MMT1 and MMTV4 were detected in the number of spontaneous metastases in the lungs of mice. An in vitro cytotoxic test and an adoptive transfer test were used to measure cytotoxic activity and the antimetastatic activity of spleen macrophages. The macrophages from mice bearing the MMT1 tumour exhibited antimetastatic activity in the adoptive transfer test, and specific and nonspecific cytotoxic activity in the in vitro test. Macrophages from mice carrying the MMTV4 tumour possessed nonspecific cytotoxic activity in vitro but did not exhibit antimetastatic activity in the adoptive transfer test. Tumours were surgically removed 13-15 days after their induction. Two weeks after the MMT1 tumour was resected, an abrupt increase in the number of spontaneous metastases in the lungs and in the lymph nodes was observed, whereas after removal of the MMTV4 tumour there were no changes in the number of lung metastases. When mice with the MMT1 tumour were given the cyclooxygenase inhibitor, indomethacin, in their drinking water, there was a significant decrease in the number of spontaneous lung metastases. Spleen macrophages from mice operated on after injection with MMT1 or MMTV4 did not possess specific cytotoxicity in the in vitro test.(ABSTRACT TRUNCATED AT 250 WORDS)