Takeya M, Yamashiro S, Yoshimura T, Takahashi K
Second Department of Pathology, Kumamoto University School of Medicine, Japan.
Lab Invest. 1995 Jun;72(6):679-88.
Malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma of adult life. Its histogenesis, however, is still a matter of debate because of its various cellular components.
To elucidate the nature of tumor cells of MFH, six human MFH cell lines were compared immunohistochemically and immunoelectron microscopically with fibrosarcoma and fibroblast cell lines. In vitro differentiation of tumor cells was evaluated after the treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA), IL-3, macrophage CSF, and granulocyte-macrophage CSF. Heterotransplantation of MFH tumor cells into nude mice and severe combined immunodeficient mice was performed to examine whether the tumor cells differentiate toward histiocytes or not. Gene expression of monocyte chemoattractant protein-1 in cultured tumor cells and transplanted tumors was also evaluated.
All MFH cell lines examined were positive for collagen type I and prolyl hydroxylase. They failed to react with most anti-myeloid mAb such as CD11c, CD14, CD15, CD33, CD35, CD45, anti-HLA-DR, and PM-2K. Several Ab, including CD13, CD32, CD68, CD71, and HAM56, were reactive with MFH cells. However, all of these Ab were also reactive with fibrosarcoma and/or fibroblastic cell lines. These data indicate that MFH cell lines possess immunophenotypic characteristics very similar to those of fibrosarcoma and fibroblastic cell lines. In vitro treatment of tumor cells with TPA, IL-3, macrophage CSF, granulocyte-macrophage CSF, or their combination did not change their immunophenotypic characteristics and did not induce differentiation toward histiocytes (macrophages). Transplantation of tumor cells into nude mice and severe combined immunodeficient mice produced tumors similar in histology to human MFH. Tumor cells in the transplanted tumors revealed the same immunophenotypic characterization that they did in vitro. No in vivo differentiation of tumor cells toward histiocytes was observed. Immunohistochemical staining with anti-mouse macrophage mAb revealed marked infiltration of macrophages of mouse origin. Quantitative immunoelectron microscopy disclosed that these cells coincided with histiocyte-like cells. Gene expression of monocyte chemoattractant protein-1 was detected in all MFH cell lines as well as in transplanted tumors.
The histiocyte-like cells in malignant fibrous histiocytoma are not a neoplastic component but rather infiltrated macrophages attracted by tumor-derived monocyte chemoattractant(s), and the tumor cells belong to a fibroblastic lineage differentiated from mesenchymal cells.
恶性纤维组织细胞瘤（MFH）是成人最常见的软组织肉瘤。然而，由于其细胞成分多样，其组织发生仍存在争议。
为阐明MFH肿瘤细胞的性质，将6种人MFH细胞系与纤维肉瘤和成纤维细胞系进行免疫组织化学和免疫电子显微镜比较。在用12 - O - 十四酰佛波醇 - 13 - 乙酸酯（TPA）、白细胞介素 - 3（IL - 3）、巨噬细胞集落刺激因子（CSF）和粒细胞 - 巨噬细胞集落刺激因子处理后，评估肿瘤细胞的体外分化情况。将MFH肿瘤细胞异种移植到裸鼠和严重联合免疫缺陷小鼠体内，以检查肿瘤细胞是否向组织细胞分化。还评估了培养的肿瘤细胞和移植肿瘤中单核细胞趋化蛋白 - 1的基因表达。
所有检测的MFH细胞系对I型胶原和脯氨酰羟化酶呈阳性。它们不与大多数抗髓系单克隆抗体反应，如CD11c、CD14、CD15、CD33、CD35、CD45、抗HLA - DR和PM - 2K。包括CD13、CD32、CD68、CD71和HAM56在内的几种抗体与MFH细胞反应。然而，所有这些抗体也与纤维肉瘤和/或成纤维细胞系反应。这些数据表明，MFH细胞系具有与纤维肉瘤和成纤维细胞系非常相似的免疫表型特征。用TPA、IL - 3、巨噬细胞CSF、粒细胞 - 巨噬细胞CSF或它们的组合对肿瘤细胞进行体外处理，并未改变其免疫表型特征，也未诱导向组织细胞（巨噬细胞）分化。将肿瘤细胞移植到裸鼠和严重联合免疫缺陷小鼠体内产生的肿瘤在组织学上与人MFH相似。移植肿瘤中的肿瘤细胞显示出与体外相同的免疫表型特征。未观察到肿瘤细胞在体内向组织细胞分化。用抗小鼠巨噬细胞单克隆抗体进行免疫组织化学染色显示有大量源自小鼠的巨噬细胞浸润。定量免疫电子显微镜显示这些细胞与组织细胞样细胞一致。在所有MFH细胞系以及移植肿瘤中均检测到单核细胞趋化蛋白 - 1的基因表达。
恶性纤维组织细胞瘤中的组织细胞样细胞不是肿瘤成分，而是被肿瘤衍生的单核细胞趋化因子吸引的浸润巨噬细胞，肿瘤细胞属于源自间充质细胞的成纤维细胞谱系。
