Macrophage-induced cytotoxicity and anti-metastatic activity of a 43-kDa human urinary protein against the Lewis tumor.

Resident, inflammatory or bone-marrow macrophages from C57Bl/6 mice incubated in vitro with a pure human urinary protein (HGP.43) decreased the growth rate of Lewis tumor cells (3LL). This inhibition of 3LL growth was the result of a cytotoxic activity of these macrophages which was independent of oxygen metabolites and nitrous oxide. Murine monoclonal antibodies (MAbs) against HGP.43 inhibited macrophage-mediated cytotoxicity. This cytotoxic activity was not due to the release of cytotoxic factors in the culture supernatant, showing that a contact between macrophages and tumor cells was required to express cytotoxicity. The presence of HGP.43 was absolutely necessary during the incubation of macrophages with target cells. In vivo, in HGP.43-treated mice, the growth of the primary tumor was not delayed but the size and number of lung metastases were significantly reduced 21 days after tumor inoculation.