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Fiscal Year 1996 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1995 : ¥1,500,000 (Direct Cost : ¥1,500,000)
The histogenesis of malignant fibrous histiocytoma (MFH) is still undetermined. We have investigated the histogenesis using cloned cell lines (MT-8, undifferentiated mesenchymal cells ; MT-9, mesenchymal cells with both natures of histiocytes and fibroblasts) derived from transplantable rat MFH.
(1) By adding hyperlipemic serum or lipopolysaccharide, both which are a potential stimulus to macrophage functions, to the medium, MT-8 and MT-9 cells enhanced their histiocytic natures.
(2) Cisplatin (anticancer drug)-resistant cell lines (MT-R8 and MT-R9) were induced from MT-8 and MT-9 cells, respectively. MT-R8 and MT-R9 cells enhanced both histiocytic and myofibroblastic natures, and further the tumors induced in syngeneic rats by MT-R9 cells showed a variety of histology : neoplastic proliferations of myofibroblasts and granular cells, osteosarcoma-like areas and areas involving many lipoblasts.
(3) We investigated the origin of "histiocytic cells" in MFH and the immunophenotypes against ra
t histiocyte-specific antibodies (ED1 and ED2). As a result, it was demonstrated that the presence of heterogeneities in the origin and immunophenotypes of the histiocytic cells.
(4) Monoclonal antibodies against MT-8 cells were produced, and the staining patterns were immunohistochemically investigated. It was clarified that there are common antigens between MFH cells and undifferentiated mesenchymal cells or macrophage liniage cells, indicating the heterogeneity in cell natures of MFH-constituting cells.
(5) We established transplantable tumors and cell lines from histiocytic sarcoma, fibrosarcoma and malignant meningioma in rats, and made comparisons of cell natures between MFH cells and these mesenchymal cell lines. The results indicated marked differences in biological natures between MFH and other mesenchymal tumor cells.
(6) On the basis of these results, it was concluded that MFH consists of mesenchymal cells at various differentiation stages shifting from undifferentiated cells to cells with both histiocytic and fibroblastic natures ; the cellular natures could be easily changed, presumably depending on microenvironmental/genetic factors. MFH cells may be a mesenchymal progenitor with multipotential differentiation. The cell natures appear to contribute to endless, unstable histology of MFH.
(7) Rat cell lines established in this study may provide useful experimental systems for studies on the histogenesis of MFH as well as mesenchymal differentiation yet undetermined. Less