Zhan Bohan, Wen Shi, Lu Jie, Shen Guiping, Lin Xianchao, Feng Jianghua, Huang Heguang
Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen 361005, China.
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, China.
Oncotarget. 2017 May 22;8(37):61264-61281. doi: 10.18632/oncotarget.18057. eCollection 2017 Sep 22.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal tumors. However, the methodological differences between orthotopic and subcutaneous xenograft (OX and SX) models will cause confusion in understanding its pathological mechanism and clinical relevance. In this study, SX and OX models were established by implanting Panc-1 and BxPC-3 cell strains under skin and on the pancreas of mice, respectively. The tumor tissue and serum samples were collected forH NMR spectroscopy followed by univariate and multivariate statistical analyses. As results, no obvious metabonomic difference was demonstrated in serum between the two models, however, the model- and cell strain-specific metabonomic differences were observed in tumor tissues. According to the KEGG analysis, ABC transporters, glycerophospholipid metabolism, purine metabolism and central carbon metabolism were identified to be the most significant components involved in metabonomic differences. Considering the methodological discrepancy in SX and OX models, such differences should be contributed to tumor microenvironment. In general, SX are not equivalent to OX models at molecular level. Subcutaneous transplantation displayed its inherent limitations though it offered a simple, inexpensive, reproducible and quantifiable advantage. And orthotopic transplantation may be favorable to simulate PDAC in patients due to its similar pathogenesis to human pancreatic cancer.
胰腺导管腺癌（PDAC）是最致命的肿瘤之一。然而，原位移植和皮下异种移植（OX和SX）模型之间的方法学差异会给理解其病理机制和临床相关性带来困惑。在本研究中，通过分别将Panc-1和BxPC-3细胞株植入小鼠皮肤下和胰腺上建立了SX和OX模型。收集肿瘤组织和血清样本进行核磁共振氢谱分析，随后进行单变量和多变量统计分析。结果显示，两种模型的血清中未表现出明显的代谢组学差异，然而，在肿瘤组织中观察到了模型和细胞株特异性的代谢组学差异。根据京都基因与基因组百科全书（KEGG）分析，ABC转运蛋白、甘油磷脂代谢、嘌呤代谢和中心碳代谢被确定为参与代谢组学差异的最显著成分。考虑到SX和OX模型的方法学差异，这种差异应归因于肿瘤微环境。总体而言，SX在分子水平上不等同于OX模型。皮下移植虽然具有简单、廉价、可重复和可量化的优点，但也显示出其固有的局限性。而原位移植由于其与人类胰腺癌相似的发病机制，可能更有利于模拟患者的PDAC。
