Histogenesis of malignant fibrous histiocytoma (MFH), with a particular reference to the relationship with mesenchymal differentiation

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Malignant fibrous histiocytoma (MFH) consists of primitive cells with potential differentiation towards various mesenchymla cells, depending on environmental conditions. In this project, in order to clarify the relationship between MFH cells and other mesenchymal cells, we compared cell characteristics by using some mesenchymal cell lines established by us. Further, we examined the distribution of positive cells against monoclonal antibodies produced by using rat MFH cell line as the immunogen.1. LPS was added to cultures of MT-9 (rat MFH cell line) and HS-P (rat histiocytic sarcoma-derived cell line), and we examined their nature. Under LPS addition, HS-P increased TNF-α production and enhanced their macrophage-like phenotypes (ED1- and ED2-positive cells). In contrast, there were no such changes in MT-9.2. Under TGF-β addition, HS-P decreased macrophage-like phenotypes, but MT-9 did not. Based on findings shown above, histiocytic cells constituting MFH differ from true macrophages.3. We succeeded in generation of rat MFH-specific monoclonal antibodies (A3, B9) by using rat MFH cell line (MT-8) as the immunogen. A3 reacted specifically to primitive mesenchymal cells among organs in the embryogenesis, and B9 labeled cytoplamic lysozyme of macrophages. These findings indicated that MFH cells share a common antigenicity with primitive mesenchymal cells, and have features similar to macrophages/histiocytes.4. In conclusion, MFH is composed of so-called fibrohistiocytes, and thus we propose the alternative term of undifferentiated mesenchymal sarcoma to the MFH.