Heterogeneity in the origin and immunophenotypes of "histiocytic" cells in transplantable rat malignant fibrous histiocytoma.

Abstract

To clarify the origin and nature of "histiocytic" cells in malignant fibrous histiocytoma (MFH), immunoreactivities to rat macrophage/histiocyte-specific monoclonal antibodies (ED1 and ED2) and monocyte chemoattractant protein-1 (MCP-1) production were investigated using rat transplantable MFH-derived cloned cells (undifferentiated MT-8 and fibrohistiocytic MT-9). In different cultures, the positive rates for ED1 and ED2 ranged from 2.5% to 26.0% in MT-8, and from 6.0% to 40.0% in MT-9. In homotransplants, ED1-positive cells were frequently observed in MT-9 tumors, but barely seen in MT-8 tumors. In both MT-8 and MT-9 tumors, ED2-positive cells were not detected within tumors. Immunophenotypic characteristics of MT-8 and MT-9 to these antibodies seemed to be easily altered depending on in vitro and in vivo conditions. By ELISA, MCP-1 was hardly detected in culture supernatants of MT-8 and MT-9, but its level was very high in sera of MT-8- and MT-9-tumor-bearing rats. In rats with these tumors, the number of circulating monocytes was significantly increased and the presence of factors stimulating macrophage proliferation was demonstrated by the colony formation assay using rat bone marrow cells. Histiocytic cells in MT-8 and MT-9 tumors that were produced in nude mice reacted only with antibody to mouse macrophage-associated antigen. This suggests the existence of non-neoplastic, infiltrated macrophages of host origin that were induced probably by MCP-1 and factors stimulating macrophage proliferation. The present studies indicate the presence of heterogeneities in the origin and immunophenotypes of "histiocytic" cells in rat MFH.