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 beta1 integrins in the growth and metastasis of a murine mammary carcinoma, SP1, and a metastatic variant, SP1-3M in vivo. CBA/J female mice bearing SP1 tumor transplants were injected with anti-beta1 integrin IgG or control nonimmune IgG (200 mug per mouse; i.p.) every two days. Animals received anti-CD4 antibody (100 mug per mouse) at time zero to suppress immunity against rabbit IgG. Outgrowth of macroscopic metastases from SP1, but not from SP1-3M primary tumors, was markedly inhibited in animals receiving anti-beta1 integrin IgG but not nonimmune IgG. To assess the stage(s) in the metastatic cascade affected, we examined the number and diameter of micrometastatic nodules in treated and untreated groups. The diameter of micrometastases was significantly reduced in SP1-tumor-bearing mice treated with anti-beta1 integrin IgG compared to control IgG, although the number of nodules per cm2 of lung sections examined remained unchanged. No change in the number or size of micrometastases in SP1-3M tumor-bearing mice was observed. No difference in the binding, or complement-mediated and antibody-dependent cell-mediated cytotoxicity of anti-beta1 integrin IgG with SP1 and SP1-3M cells was detected. The results suggest that under these conditions anti-beta1 integrin inhibits metastatic tumor growth in lung tissue, but has minimal effect on intravasation, adhesion to target organs and extravasation.