Background: Malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma of adult life. Its histogenesis, however, is still a matter of debate because of its various cellular components.
Experimental design: To elucidate the nature of tumor cells of MFH, six human MFH cell lines were compared immunohistochemically and immunoelectron microscopically with fibrosarcoma and fibroblast cell lines. In vitro differentiation of tumor cells was evaluated after the treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA), IL-3, macrophage CSF, and granulocyte-macrophage CSF. Heterotransplantation of MFH tumor cells into nude mice and severe combined immunodeficient mice was performed to examine whether the tumor cells differentiate toward histiocytes or not. Gene expression of monocyte chemoattractant protein-1 in cultured tumor cells and transplanted tumors was also evaluated.
Results: All MFH cell lines examined were positive for collagen type I and prolyl hydroxylase. They failed to react with most anti-myeloid mAb such as CD11c, CD14, CD15, CD33, CD35, CD45, anti-HLA-DR, and PM-2K. Several Ab, including CD13, CD32, CD68, CD71, and HAM56, were reactive with MFH cells. However, all of these Ab were also reactive with fibrosarcoma and/or fibroblastic cell lines. These data indicate that MFH cell lines possess immunophenotypic characteristics very similar to those of fibrosarcoma and fibroblastic cell lines. In vitro treatment of tumor cells with TPA, IL-3, macrophage CSF, granulocyte-macrophage CSF, or their combination did not change their immunophenotypic characteristics and did not induce differentiation toward histiocytes (macrophages). Transplantation of tumor cells into nude mice and severe combined immunodeficient mice produced tumors similar in histology to human MFH. Tumor cells in the transplanted tumors revealed the same immunophenotypic characterization that they did in vitro. No in vivo differentiation of tumor cells toward histiocytes was observed. Immunohistochemical staining with anti-mouse macrophage mAb revealed marked infiltration of macrophages of mouse origin. Quantitative immunoelectron microscopy disclosed that these cells coincided with histiocyte-like cells. Gene expression of monocyte chemoattractant protein-1 was detected in all MFH cell lines as well as in transplanted tumors.
Conclusions: The histiocyte-like cells in malignant fibrous histiocytoma are not a neoplastic component but rather infiltrated macrophages attracted by tumor-derived monocyte chemoattractant(s), and the tumor cells belong to a fibroblastic lineage differentiated from mesenchymal cells.