Kawashima Maki, Ide Mika, Nakanishi Masako, Kuwamura Mitsuru, Kumagai Daijiro, Yamate Jyoji
Laboratory of Veterinary Pathology, Graduate School of Agriculture and Biological Sciences, Osaka Prefecture University, Gakuencho 1-1, Sakai, Osaka 599-8531, Japan.
Virchows Arch. 2003 Feb;442(2):141-50. doi: 10.1007/s00428-002-0716-8. Epub 2002 Oct 15.
Basically, dendritic cell-derived sarcomas are characterized by expression of major histocompatibility complex class-II molecules, but the biological properties of the tumor cells remain to be elucidated. Recently, we established a novel transplantable cell line (KB-D8) from a dendritic cell sarcoma found in an F344 rat. In the present study, we investigated immunophenotypical changes of KB-D8 tumor cells and tumor-associated macrophages (TAMs) appearing in relation to tumor development in syngeneic F344 rats. A number of neoplastic cells in 0.5-cm-diameter KB-D8 tumors showed immunoreactions to OX6 (specific for rat antigen-presenting cells), ED1 (for rat exudate macrophages), and ED2 (for rat resident macrophages), and 72% and 11% of the OX6+ cells were double-immunostained with ED1 and ED2, respectively. Interestingly, the immunoreactions to these antibodies were gradually reduced with increasing size of KB-D8 tumors of 1-, 2-, and 3-cm diameter. These findings indicated that immunophenotypes of dendritic cell-derived sarcomas may be changeable depending on microenvironmental conditions in vivo. Many TAMs seen outside KB-D8 tumors reacted to OX6, ED1, and ED2; the numbers of TAMs immunopositive for these antibodies also decreased as the tumor grew. Similarly, the earlier temporary increase and subsequent gradual decrease in ED2+ and OX6+ cell numbers were observed in the spleen and liver of KB-D8-bearing rats. The reverse-transcription polymerase chain reaction showed mRNA expressions of granulocyte/macrophage-colony stimulating factor, monocyte-chemoattractant protein-1, and osteopontin in KB-D8 tumor tissues. Although the functional roles (biphasic roles: suppressing or promoting) of these factors should be investigated further in relation to tumor development, the factors might be partially responsible for the TAM reactions. KB-D8 would be a useful experimental model to investigate the biological characteristics of dendritic cell sarcomas and tumor immunology in the host.
基本上，树突状细胞衍生肉瘤的特征是主要组织相容性复合体II类分子的表达，但肿瘤细胞的生物学特性仍有待阐明。最近，我们从一只F344大鼠身上发现的树突状细胞肉瘤中建立了一种新型可移植细胞系（KB-D8）。在本研究中，我们调查了同基因F344大鼠中与肿瘤发展相关的KB-D8肿瘤细胞和肿瘤相关巨噬细胞（TAM）的免疫表型变化。直径0.5厘米的KB-D8肿瘤中的许多肿瘤细胞对OX6（对大鼠抗原呈递细胞特异）、ED1（对大鼠渗出性巨噬细胞）和ED2（对大鼠驻留巨噬细胞）呈免疫反应，并且分别有72%和11%的OX6+细胞与ED1和ED2进行了双重免疫染色。有趣的是，随着KB-D8肿瘤直径从1厘米增大到2厘米再到3厘米，对这些抗体的免疫反应逐渐减弱。这些发现表明，树突状细胞衍生肉瘤的免疫表型可能会根据体内微环境条件而变化。在KB-D8肿瘤外部看到的许多TAM对OX6、ED1和ED2有反应；随着肿瘤生长，对这些抗体呈免疫阳性的TAM数量也减少。同样，在携带KB-D8的大鼠的脾脏和肝脏中观察到ED2+和OX6+细胞数量早期暂时增加，随后逐渐减少。逆转录聚合酶链反应显示KB-D8肿瘤组织中有粒细胞/巨噬细胞集落刺激因子、单核细胞趋化蛋白-1和骨桥蛋白的mRNA表达。尽管这些因子在肿瘤发展中的功能作用（双相作用：抑制或促进）应进一步研究，但这些因子可能部分负责TAM反应。KB-D8将是研究宿主中树突状细胞肉瘤的生物学特性和肿瘤免疫学的有用实验模型。
