An experimental model for in vivo distant metastasis of human xenografts subcutaneously transplanted in imuune-deficient mice

在这项研究中，我们建立了人类异种移植物在严重联合免疫缺陷（SCID）小鼠体内远处转移的实验模型。我们检测了50种不同人类肿瘤异种移植体的非转移性（NM23）基因表达水平。我们分离了LC-11JCK和LC-17JCK的人肺癌异种移植物。LC-17JCK不表达NM23基因转录本，LC-11JCK表达NM23基因。将异种移植物皮下移植到SCID小鼠体内。移植后对小鼠进行尸检，以检测远处转移到肺或肝脏的情况。我们还检测了血管内皮生长因子的表达水平。LC-17JCK移植3个月后出现明显的肝、肺转移。然而，LC-11JCK在小鼠中未表现出任何远处转移。我们还研究了LC-17在SCID/北京小鼠中的转移发生率。SCID/beige小鼠的远端转移明显增加。在SCID/beige小鼠中，自然杀伤细胞的功能也受到抑制。LC-17异种移植物也显示VEGF基因转录物水平升高。提示NM-23基因和VEGF基因的表达水平可能与人肺癌移植物体内远处转移有关。该实验模型采用重度联合免疫缺陷小鼠作为研究肿瘤转移的有力系统。

In this study, we established an experimental model for in vivo distant metastasis of human xenografts in severe combined immune deficient (SCID) mice. We examined non-metastatic (NM23) gene expression levels in the total 50 of various kinds of human tumor xenograts. We isolated human lung cancer xenografts LC-11JCK and LC-17JCK.The LC-17JCK did not express NM23 gene transcripts, whereas the LC-11JCK showed remarkable expression of NM23 gene. The xenogarafts were subcutaneously transplanted into the SCID mice. The mice were autopsied after transplantation to detect distant metastases into the lung or liver. We also examined the expression levels of vascular endothelial growth factor.The human lung cancer xenograft LC-17JCK showed remarkable liver and lung metastases 3 months after transplantation. However, the LC-11JCK did not show any distant metastasis in the mice. We also examined the metastatic incidence of the LC-17 in the SCID/beig mice. The distant metastasis is significantly increased in the SCID/beige mice. The function of natural killer cells are additionally suppressed in the SCID/beige mice. The LC-17 xenografts also showed an increased level of VEGF gene transcripts.These results suggest the expression levels of NM-23 gene and VEGF gene may related to distant metastases of the human lung cancer xenografts in vivo. This experimental model using severe combined immune deficient mice are potent system for the research of cancer metastasis.