Development of a unique mouse model for pancreatic cancer lymphatic metastasis
Development of a unique mouse model for pancreatic cancer lymphatic metastasis
复制标题
开发胰腺癌淋巴转移的独特小鼠模型
DOI：
10.3892/ijo.2012.1613
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发表时间：
2012-11-01
影响因子：
5.2
通讯作者：
Yu, Xianjun
中科院分区：
文献类型：
--
作者：
Long, Jiang;Luo, Guopei;Yu, Xianjun
胰腺癌淋巴结转移是预后不良的预测因子。然而，分子机制在很大程度上是未知的，因此，适当的细胞系和实验模型的发展是至关重要的未来的调查。本研究的目的是建立一种具有高淋巴道转移潜能的胰腺癌细胞和小鼠模型，为深入研究胰腺癌淋巴道转移的机制奠定基础。BxPC-3-LN亚系来源于BxPC-3人胰腺癌细胞系，通过足垫注射在裸鼠中连续传代建立。肿瘤细胞植入后8周，该亚系能够在100%的受体小鼠中发展出显著的淋巴转移。与亲本BxPC-3细胞相比，BxPC-3-LN细胞具有更强的侵袭性，显示侵袭性超微结构，迁移和侵袭能力增强，并具有耐药性。基因芯片检测显示BxPC-3-LN细胞中MMP 14、MMP 24、MIF和ADRM 1表达上调，TGF β 2和ROBO 1表达下调。因此，新选择的BxPC-3-LN亚系可以作为进一步研究胰腺癌淋巴转移的独特模型。
Lymphatic metastasis of pancreatic cancer is a predictor of poor prognosis. However, the molecular mechanisms are largely unknown, thus, making the development of appropriate cell lines and experimental models critically important for future investigations. The purpose of the present study was to establish a 'pancreatic cancer cell and mouse model with high lymphatic metastasis potential' for in-depth study of the underlying mechanisms. The BxPC-3-LN subline, derived from the BxPC-3 human pancreatic cancer cell line, was established through serial passages in nude mice via footpad injections. The subline was able to develop notable lymphatic metastases in 100% of the recipient mice 8 weeks after tumor cell implantation. Compared with the parental BxPC-3 cells, BxPC-3-LN cells were more aggressive, displaying invasive ultrastructure, increased migration and invasion ability, and chemoresistance. Metastasis-related gene alteration including upregulation of MMP14, MMP24, MIF and ADRM1, and downregulation of TGFB2 and ROBO1 were also observed in BxPC-3-LN cells by cDNA microarrays. Thus, the newly selected BxPC-3-LN subline can serve as a unique model for further study of lymphatic metastasis of pancreatic cancer.