PROGRESSIVE GROWTH IN IMMUNODEFICIENT MICE AND HOST-CELL RECRUITMENT BY MOUSE ENDOTHELIAL-CELLS TRANSFORMED BY POLYOMA MIDDLE-SIZED T-ANTIGEN - IMPLICATIONS FOR THE PATHOGENESIS OF OPPORTUNISTIC VASCULAR TUMORS
PROGRESSIVE GROWTH IN IMMUNODEFICIENT MICE AND HOST-CELL RECRUITMENT BY MOUSE ENDOTHELIAL-CELLS TRANSFORMED BY POLYOMA MIDDLE-SIZED T-ANTIGEN - IMPLICATIONS FOR THE PATHOGENESIS OF OPPORTUNISTIC VASCULAR TUMORS
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DOI：
10.1073/pnas.91.15.7291
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发表时间：
1994-07-19
影响因子：
11.1
通讯作者：
VECCHI, A
中科院分区：
文献类型：
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作者：
GARLANDA, C;PARRAVICINI, C;VECCHI, A
利用一种编码多瘤中等大小T抗原的逆转录病毒构建物，从C57BL/6小鼠的心脏（H5V）、脑（B9V）和全胚胎（E10V）中生成转化内皮细胞系。当注射到同基因受体时，H5V和较少研究的B9V和E10V细胞引起血管肿瘤，根据接种细胞的数量，肿瘤消退或发展，导致宿主死亡。当将H5V细胞注射到免疫缺陷小鼠体内时，接种观察到肿瘤，在免疫正常的受体中未形成病变，也未发生倒退。用抗lfa -1、抗thy -1.2和抗cd8抗体治疗可消除排斥反应；抗cd4是一种不太有效的耐药性抑制剂。进展性肿瘤动物在裸鼠中表现出不同器官的继发性病变，并明显累及皮肤。组织学上，肿瘤表现为血管瘤，区域类似卡波西肉瘤。血管腔隙内的细胞具有注射型H5V细胞的形态学特征。病变的特点是明显的新生血管和单核细胞浸润。Southern blot杂交分析显示，肿瘤肿块中约5%的细胞是移植的H5V细胞。因此，H5V转化的内皮细胞系引起血管病变，这些病变在很大程度上是通过宿主细胞的募集来维持的，并且仅在免疫功能低下的宿主中表现出完全的恶性行为。肿瘤是由一小部分转化细胞维持的，这些细胞只在免疫缺陷的宿主中招募宿主元素并表现出完全的恶性行为，这一假设可以解释人类某些血管肿瘤的几个特征。
A retroviral construct encoding polyoma middle-sized T antigen was used to generate transformed endothelial cell lines from heart (H5V), brain (B9V), and whole-embryo (E10V) of C57BL/6 mice. When injected into syngeneic recipients, H5V and the less studied B9V and E10V cells caused vascular tumors which, depending on the number of cells inoculated, regressed or progressed, leading to death of the host. When H5V cells were injected into immunodeficient mice, tumors were observed with inocula which did not form lesions in immunocompetent recipients and regression did not occur. Treatment with anti-LFA-1, anti-Thy-1.2, and anti-CD8 antibodies abolished rejection; anti-CD4 was a somewhat less effective inhibitor of resistance. Animals with progressive tumors exhibited secondary lesions in various organs with prominent skin involvement in nude mice. Histologically, the tumors had the appearance of a hemangioma, with areas resembling Kaposi sarcoma. Cells lining vascular lacunae had the morphological features of injected H5V cells. The lesions were characterized by prominent neovascularization and mononuclear cell infiltration. Southern blot hybridization analysis revealed that approximate to 5% of the cells in the tumor mass were transplanted H5V cells. Thus, the H5V transformed endothelial line causes vascular lesions that are sustained to a large extent by recruitment of host cells and manifests full malignant behavior only in immunocompromised hosts. The hypothesis of a tumor sustained by a minute proportion of transformed cells, which recruit host elements and express full malignant behavior only in immunodeficient hosts, would account for several features of some vascular neoplasms in man.