Lunardi-Iskandar Y, Wernert N, Cong T H, Samnang S, Bryant J L, Vandenbunder B, Stéhelin D
Institute of Human Virology, Medical Biotechnology Center, University of Maryland at Baltimore, USA.
J Hum Virol. 1999 Sep-Oct;2(5):315-7.
Kaposi's sarcoma (KS) is an acquired immunodeficiency syndrome (AIDS)-defining neoplasm histologically characterized by proliferation of spindle cells, inflammatory cells, and abundant neovascularization. When the malignant cell line KSY-1 derived from an AIDS-KS tumor is transplanted subcutaneously into nude mice, prominent neovascular features develop. Using this mouse model of neoplastic KS, we set out to determine, using c-ets 1 markers specific for mouse or human tissues, whether vascular growth and inflammatory infiltrate induced by the transplanted KSY-1 cells is of host cell or transplant origin.
STUDY DESIGN/METHODS: KS tumors were induced by subcutaneous inoculation of 5 x 10(6) KSY-1 cells/200 microL in immunodeficient mice, and species-specific mouse and human riboprobes of the c-ets 1 protooncogene were used for in situ hybridization to define cell of origin.
Five different tumors were examined. Tissue sections from all cases were hybridized with radiolabeled riboprobes for the presence of both mouse and human c-ets 1 mRNA. Tumor cells were labeled with the human c-ets 1 probe, whereas neovascular and inflammatory tissues were of mouse origin.
The finding that vascular but not tumor cells are of host origin supports the model of tumor-induced vascularization via a mechanism of tumor cell-derived cytokine-medicated pathogenesis.
卡波西肉瘤(KS)是一种获得性免疫缺陷综合征(AIDS)相关肿瘤,其组织学特征为梭形细胞、炎症细胞增殖以及丰富的新生血管形成。当将源自AIDS-KS肿瘤的恶性细胞系KSY-1皮下移植到裸鼠体内时,会出现明显的新生血管特征。利用这种肿瘤性KS小鼠模型,我们使用针对小鼠或人类组织的c-ets 1标记物,来确定移植的KSY-1细胞诱导的血管生长和炎症浸润是宿主细胞来源还是移植来源。
研究设计/方法:通过在免疫缺陷小鼠皮下接种5×10⁶个KSY-1细胞/200微升来诱导KS肿瘤,并使用c-ets 1原癌基因的物种特异性小鼠和人类核糖探针进行原位杂交,以确定细胞来源。
检查了5个不同的肿瘤。所有病例的组织切片均与放射性标记的核糖探针杂交,以检测小鼠和人类c-ets 1 mRNA的存在。肿瘤细胞用人类c-ets 1探针标记,而新生血管和炎症组织则来源于小鼠。
血管而非肿瘤细胞来源于宿主这一发现支持了肿瘤通过肿瘤细胞衍生的细胞因子介导的发病机制诱导血管生成的模型。