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

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07660424/
• 关键词: malignant fibrous histiocytoma; mesenchymal progenitor; mesenchymal tumor; myofibroblastic cell; histiocyte; histogenesis; multipotential differentiation; rat experimental model; 悪意線維性組織球腫

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)的组织起源尚不清楚。我们用可移植的大鼠骨髓间充质细胞克隆细胞系(MT-8，未分化间充质细胞；MT-9，兼具组织细胞和成纤维细胞特性的间充质细胞)研究了组织发生。(1)通过向培养液中加入对巨噬细胞功能有潜在刺激作用的高脂血清或脂多糖，MT-8和MT-9细胞增强了其组织细胞特性。(2)从MT-8和MT-9细胞分别诱导出顺铂耐药细胞系(MT-R8和MT-R9)。MT-R8和MT-R9细胞增强了组织细胞和肌成纤维细胞的特性，MT-R9细胞诱导的同基因大鼠肿瘤表现为多种组织学变化：肌成纤维细胞和颗粒细胞的肿瘤性增殖，骨肉瘤样区域和累及多个脂肪母细胞的区域。(3)我们研究了MFH中“组织细胞”的来源和抗ra…的免疫表型更多的组织细胞特异性抗体(ED1和ED2)。结果表明，MT-8细胞在来源和免疫表型上存在异质性。(4)制备了抗MT-8细胞的单抗，并对其染色模式进行了免疫组织化学研究。MFH细胞与未分化间充质细胞或巨噬细胞系之间存在共同的抗原，表明MFH构成细胞的细胞性质具有异质性。(5)建立了大鼠组织细胞肉瘤、纤维肉瘤和恶性脑膜瘤的移植瘤和细胞系，并与这些间充质细胞系进行了细胞特性的比较。结果表明，MFH的生物学特性与其他间充质肿瘤细胞有显著差异。(6)根据上述结果，MFH由处于不同分化阶段的间充质细胞从未分化的细胞向兼具组织细胞和成纤维细胞性质的细胞转变，其细胞性质很容易发生改变，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潜能的间充质祖细胞。这些细胞的性质似乎有助于MFH无穷无尽的、不稳定的组织学。(7)本研究建立的大鼠细胞系可能为MFH的组织发生以及间充质分化的研究提供有用的实验系统，但尚未确定。较少

项目成果

yamato J: "Phenotypic modulation in cisplatin-resistant cloned cells derived from transplantable rat malignant fibrous histiocytoma" Pathology International. 46. 557-567 (1996)

yamato J：“源自可移植大鼠恶性纤维组织细胞瘤的顺铂耐药克隆细胞的表型调节”国际病理学。

Yamate J et al: "Phenotypic changes in lipopolysaccharide-treated cloned cells derived from transplantable rat malignant fibrous histiocytoma" The Journal of Veterinary Medical Science. 58. 1017-1020 (1996)

Yamate J 等人：“源自可移植大鼠恶性纤维组织细胞瘤的经脂多糖处理的克隆细胞的表型变化”《兽医医学科学杂志》。

Yamate J: "Heterogeneity in the origin and immunophenotypes of "histiocytic" cells in transplantable rat malignant fibrous histiocytoma" The Journal of Veterinary Medical Science. 58. 603-609 (1996)

Yamate J：“可移植大鼠恶性纤维组织细胞瘤中“组织细胞”细胞的起源和免疫表型的异质性”《兽医医学科学杂志》。

Yamate J et al: "Phenotypic modulation in cisplatin-resistant cloned cells derived from transplantable rat malignant fibrous histiocytoma" Pathology International. 46. 557-567 (1996)

Yamate J 等人：“源自可移植大鼠恶性纤维组织细胞瘤的顺铂耐药克隆细胞的表型调节”国际病理学。

Tsujino K: "Establishment and characterization of cell lines derived from a transplantable rat malignant meningioma: morphological heterogeneity and production of nerve growth factor (NGF)" Acta Neuropathologica. (in press). (1997)

Tsujino K：“源自可移植大鼠恶性脑膜瘤的细胞系的建立和表征：形态异质性和神经生长因子（NGF）的产生”《神经病理学报》。