Metastasis-associated gene expression profile of liver and subcutaneous lesions derived from mouse pheochromocytoma cells
Metastasis-associated gene expression profile of liver and subcutaneous lesions derived from mouse pheochromocytoma cells
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DOI：
10.1002/mc.20388
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发表时间：
2008-04-01
影响因子：
4.6
通讯作者：
Pacak, Karel
中科院分区：
文献类型：
--
作者：
Ohta, Shoichiro;Lai, Edwin W.;Pacak, Karel
转移性癌症的发展与特定基因和细胞调节途径的过表达或下调相关。这些基因和途径中的一些可能参与肿瘤细胞的侵袭和扩散，而另一些可能促进细胞在特定远端部位的接种、存活或生长。在这项调查中，非转移性肿瘤的基因表达谱皮下注射小鼠嗜铬细胞瘤细胞（MPC）产生的静脉注射细胞产生的肝肿瘤进行了比较。将两者与培养的亲本细胞系进行比较。肝脏中的肿瘤具有与自然转移的嗜铬细胞瘤相似的扩散途径、解剖分布和生长环境，而静脉内注射细胞绕过了原发性肿瘤自发发生的转移的初始步骤。与培养的细胞相比，8个基因在肝肿瘤中上调，15个在皮下肿瘤中上调，7个在两者中上调。使用定量实时PCR，五个基因（Metap 2，Reck，S100 a4，Timp 2和Timp 3）的表达被证实在肝肿瘤中显著低于皮下肿瘤。这些基因的下调此前已被认为与嗜铬细胞瘤的恶性程度有关。这些研究结果表明，不同的微环境可以差异影响转移相关基因在嗜铬细胞瘤的表达，这些基因的过度表达或低表达不需要存在时，肿瘤细胞最初传播。通过静脉注射MPC细胞形成的肿瘤的肝定位和肿瘤的基因表达谱类似于自然发生的嗜铬细胞瘤转移支持使用该模型来研究嗜铬细胞瘤转移。(C)2007 Wiley-Liss，Inc.
The development of metastatic cancer is associated with overexpression or downregulation of specific genes and cell regulatory pathways. Some of these genes and pathways may be involved in invasion and dissemination of tumor cells, while others may promote seeding, survival or growth of cells at specific distant sites. In this investigation, gene expression profiles of nonmetastasizing tumors generated by injecting mouse pheochromocytoma cells (MPCs) subcutaneously were compared to those of liver tumors generated by injecting the cells intravenously. Both were compared to the cultured parental cell line. Tumors in the liver have a route of spread, anatomical distribution, and growth environment similar to naturally metastasizing pheochromocytomas, while intravenous injection of cells bypasses the initial steps of metastasis occurring spontaneously from a primary tumor. Eight genes were upregulated in liver tumors, 15 in subcutaneous tumors and seven in both compared to the cultured cells. Using quantitative real-time PCR, expression of five genes (Metap2, Reck, S100a4, Timp2, and Timp3) was verified as significantly lower in liver tumors than in subcutaneous tumors. Downregulation of these genes has been previously been associated with malignancy of pheochromocytomas. These findings indicate that different microenvironments can differentially affect the expression of metastasis-related genes in pheochromocytomas, and that overexpression or underexpression of these genes need not be present when the tumor cells are initially disseminated. The hepatic localization of tumors formed by intravenously injected MPC cells and the tumors' gene expression profile resembling that of naturally occurring pheochromocytoma metastases support the use of this model to study pheochromocytoma metastasis. (C) 2007 Wiley-Liss, Inc.