Orthotopic implantation mouse model and cDNA microarray analysis indicates several genes potentially involved in lymph node metastasis of colorectal cancer
Orthotopic implantation mouse model and cDNA microarray analysis indicates several genes potentially involved in lymph node metastasis of colorectal cancer
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DOI：
10.1111/j.1349-7006.2008.00725.x
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发表时间：
2008-04-01
期刊：
影响因子：
5.7
通讯作者：
Sasaki, Iwao
中科院分区：
文献类型：
--
作者：
Sasaki, Hiroyuki;Miura, Koh;Sasaki, Iwao
在结直肠癌（CRC）患者中，转移到区域淋巴结（LN）是癌症扩散的重要第一步。为了确定可能参与结直肠癌淋巴结转移的基因，我们分析了淋巴结转移的原位种植小鼠模型与22结直肠癌细胞系使用Matrigel，细胞外基质蛋白来源于小鼠肉瘤，并结合这些细胞系的cDNA微阵列的基因表达谱的数据。通过该植入分析，在228只原位植入小鼠中LN转移的发生率为60%，并且在细胞系之间从100%变化到0%。KM 12 c和克隆A在所有原位植入小鼠中显示LN转移，但DLD-1、HCT-8和SW 948根本不显示LN转移。相比之下，在22个CRC细胞系中肝和肺转移的发生率分别为13%和1%。将这些数据与体外cDNA微阵列相结合，我们分离出636个根据LN转移发生率差异表达的基因。在这些基因中，环指蛋白125（RNF 125）的表达水平，以前被称为T细胞活化中的E3泛素连接酶，在具有LN转移的III期CRC患者和没有LN转移的II期患者的原发性肿瘤之间显著不同。总之，Matrigel原位移植小鼠模型是有用的，我们分离了候选基因，如RNF 125，可能在结直肠癌细胞的LN转移中发挥重要作用。
In colorectal cancer (CRC) patients, metastasis to the regional lymph node (LN) is an important first step in the dissemination of cancers. To identify the genes possibly involved in LN metastasis of CRC, we analyzed LN metastases in an orthotopic implantation mouse model with 22 CRC cell lines using Matrigel, an extracellular matrix protein derived from mice sarcoma, and combined the data with gene expression profiles of cDNA microarray of those cell lines. With this implantation analysis, the incidence of LN metastasis was 60% in 228 orthotopically implanted mice and varied from 100% to 0% among the cell lines. KM12c and Clone A showed LN metastasis in all orthotopically implanted mice, but DLD-1, HCT-8, and SW948 did not show LN metastases at all. In contrast, the incidence of liver and lung metastasis in 22 CRC cell lines was 13% and 1%, respectively. Combining those data with cDNA microarray in vitro, we isolated 636 genes that were differentially expressed depending on the incidence of LN metastasis. Among those genes, the expression level of ring finger protein 125 (RNF125), previously known as an E3 ubiquitin ligase in T cell activation, was significantly different between primary tumors in Stage III CRC patients with LN metastasis and Stage II patients without LN metastasis. In conclusion, the orthotopic implantation mice model with Matrigel was useful, and we isolated candidate genes such as RNF125 that possibly play an important role in LN metastasis of CRC cells.