Macrophage‐induced cytotoxicity and anti‐metastatic activity of a 43‐kDa human urinary protein against the lewis tumor

Abstract
Resident, inflammatory or bone‐marrow macrophages from C57BI/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.