THE HISTOGENESIS OF MALIGNANT FIBROUS HISTIOCYTOMA (MFH), WITH THE SPECIAL REFERENCE TO MULTIPOTENTIAL DIFFERENTIATION OF MFH CELLS

恶性纤维组织细胞瘤（MFH）的组织发生，特别是 MFH 细胞的多向分化

基本信息

批准号：
07660424
负责人：
YAMATE Jyoji
金额：
$ 1.28万
依托单位：
OSAKA PREFECTURE UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

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 … More 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

恶性纤维组织细胞瘤（MFH）的组织发生尚未确定，我们使用源自可移植大鼠 MFH 的克隆细胞系（MT-8，未分化间充质细胞；MT-9，具有组织细胞和成纤维细胞性质的间充质细胞）研究了其组织发生。 (1) 通过添加高脂血症血清或脂多糖，这两者都是潜在的刺激巨噬细胞功能，对培养基，MT-8和MT-9细胞增强其组织细胞性质。（2）从MT-8和MT-诱导顺铂（抗癌药物）耐药细胞系（MT-R8和MT-R9） MT-R8和MT-R9细胞分别增强了组织细胞和肌纤维母细胞的性质，并进一步增强了MT-R9在同基因大鼠中诱导的肿瘤。细胞表现出多种组织学特征：肌成纤维细胞和颗粒细胞的肿瘤性增殖、骨肉瘤样区域和涉及许多脂肪母细胞的区域。(3) 我们研究了 MFH 中“组织细胞”的起源以及针对组织细胞特异性的免疫表型。结果表明，抗体的来源和免疫表型存在异质性。 (4)制备抗MT-8细胞的单克隆抗体，并进行免疫组织化学染色分析，发现MFH细胞与未分化间充质细胞或巨噬细胞系细胞之间存在共同抗原，表明细胞性质的异质性。 (5)我们建立了组织细胞肉瘤、纤维肉瘤的可移植肿瘤和细胞系并比较了MFH细胞与这些间充质细胞系的细胞性质，结果表明MFH与其他间充质肿瘤细胞在生物学性质上存在显着差异。(6)根据这些结果得出结论。 MFH 由处于不同分化阶段的间充质细胞组成，从未分化细胞转变为具有组织细胞和成纤维细胞性质的细胞，细胞性质可能很容易改变，这可能取决于微环境/遗传因素。MFH细胞可能是具有多向分化能力的间充质祖细胞。细胞性质似乎有助于MFH的无限、不稳定的组织学。(7)本研究中建立的大鼠细胞系可能为组织发生的研究提供有用的实验系统。 MFH 以及间质分化尚未确定。