Toxicology and Chemotherapy Unit, German Cancer Research Center, G401, Heidelberg, Germany.
Oncol Rep. 2012 Dec;28(6):2177-87. doi: 10.3892/or.2012.2049. Epub 2012 Sep 20.
Owing to aggressiveness and chemoresistance, pancreatic ductal adenocarcinoma (PDAC) is characterised by a poor prognosis. To address this disease-spe-cific dilemma we aimed to establish animal models, which can be used for identifying new specific tumor markers, as well as serving as tools for potential therapeutic approaches. From a panel of sixteen pancreatic cancer cell lines, two human (Suit2-007 and Suit2-013) and a rat (ASML) cell line were selected for their properties to grow in the liver of male RNU rats and mimic liver metastasis of PDAC. For better monitoring of metastatic tumor growth in vivo, all three pancreatic cancer cell lines were stably transfected with eGFP and luciferase marker genes. In addition, the mRNA expression profile of 13 human PDAC cell lines was analyzed by BeadChip array analysis. Only 33 genes and 5 signaling pathways were identified as significantly associated with the ability of the cell lines to grow initially and/or consistently in rat liver. Only a minority of these genes (osteopontin, matrix metalloproteinase-1 and insulin-like growth factor 1) has been intensively studied and shown to be closely related to cancer progression. The function of the remaining 30 genes ranges from moderate to poorly investigated, and their function in cancer progression is still unclear. The ensuing three pancreatic cancer liver metastasis models vary in their aggressiveness and macroscopic growth. They will be used for preclinical evaluation of new therapeutic approaches aiming at the genes identified.
由于侵袭性和化疗耐药性,胰腺导管腺癌 (PDAC) 的预后较差。为了解决这一特定于疾病的难题,我们旨在建立动物模型,这些模型可用于鉴定新的特定肿瘤标志物,并作为潜在治疗方法的工具。从十六种胰腺癌细胞系中,选择了两种人(Suit2-007 和 Suit2-013)和一种大鼠(ASML)细胞系,其特性是在雄性 RNU 大鼠肝脏中生长,并模拟 PDAC 的肝转移。为了更好地监测体内转移性肿瘤的生长,将三种胰腺癌细胞系均稳定转染了 eGFP 和荧光素酶标记基因。此外,通过 BeadChip 芯片分析还分析了 13 个人胰腺癌细胞系的 mRNA 表达谱。只有 33 个基因和 5 个信号通路被确定与细胞系最初和/或持续在大鼠肝脏中生长的能力显著相关。这些基因中只有少数(骨桥蛋白、基质金属蛋白酶 1 和胰岛素样生长因子 1)已经被深入研究,并被证明与癌症进展密切相关。其余 30 个基因的功能从中度到研究甚少,其在癌症进展中的功能尚不清楚。随后的三种胰腺癌肝转移模型在侵袭性和宏观生长方面存在差异。它们将用于针对所鉴定基因的新治疗方法的临床前评估。