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

恶性纤维组织细胞瘤（MFH）由原始细胞组成，根据环境条件，这些原始细胞具有向各种间充质细胞分化的潜能。本课题利用我们建立的间充质细胞系，比较了MFH细胞与其他间充质细胞的特性，以阐明MFH细胞与其他间充质细胞的关系。进一步，我们检测了以大鼠MFH细胞系为免疫原制备的单克隆抗体的阳性细胞分布.将LPS加入MT-9（大鼠MFH细胞系）和HS-P（大鼠组织细胞肉瘤衍生细胞系）的培养物中，并检查其性质。在LPS添加下，HS-P增加TNF-α的产生并增强其巨噬细胞样表型（ED 1和ED 2阳性细胞）。相比之下，MT-9.2中没有这种变化。加入TGF-β后，HS-P减少巨噬细胞样表型，而MT-9则无此作用。基于上述发现，构成MFH的组织细胞不同于真正的巨噬细胞。以大鼠MFH细胞系MT-8为免疫原，成功地制备了大鼠MFH特异性单克隆抗体（A3、B 9）。A3特异性反应于胚胎发育器官间的原始间充质细胞，B 9特异性反应于巨噬细胞胞质溶菌酶。这些结果表明MFH细胞与原始间充质细胞具有共同的抗原性，并具有类似于巨噬细胞/组织细胞的特征.总之，MFH是由所谓的纤维组织细胞，因此，我们建议的未分化间叶肉瘤的MFH的替代术语。

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.