ANTI-BETA(1)-INTEGRIN IGG INHIBITS PULMONARY MACROMETASTASIS AND THE SIZE OF MICROMETASTASES FROM A MURINE MAMMARY-CARCINOMA

In the present report, we investigated the possible importance of beta 1 integrins in the growth and metastasis of a murine mammary carcinoma , SP1, and a metastatic variant, SP1-3M in vivo. CBA/J female mice bea ring SP1 tumor transplants were injected with anti-beta1 integrin IgG or control nonimmune IgG (200 mug per mouse; i.p.) every two days. Ani mals received anti-CD4 antibody (100 mug per mouse) at time zero to su ppress immunity against rabbit IgG. Outgrowth of macroscopic metastase s from SP1, but not from SP1-3M primary tumors, was markedly inhibited in animals receiving anti-beta1 integrin IgG but not nonimmune IgG. T o assess the stage(s) in the metastatic cascade affected, we examined the number and diameter of micrometastatic nodules in treated and untr eated groups. The diameter of micrometastases was significantly reduce d in SP1-tumor-bearing mice treated with anti-beta1 integrin IgG compa red to control IgG, although the number of nodules per cm2 of lung sec tions examined remained unchanged. No change in the number or size of micrometastases in SP1-3M tumor-bearing mice was observed. No differen ce in the binding, or complement-mediated and antibody-dependent cell- mediated cytotoxicity of anti-beta1 integrin IgG with SP1 and SP1-3M c ells was detected. The results suggest that under these conditions ant i-beta1 integrin inhibits metastatic tumor growth in lung tissue, but has minimal effect on intravasation, adhesion to target organs and ext ravasation.