Comparison of Tumour-Specific Phenotypes in Human Primary and Expandable Pancreatic Cancer Cell Lines

作者全名："Guo, Feng; Kan, Kejia; Rueckert, Felix; Rueckert, Wolfgang; Li, Lin; Eberhard, Johannes; May, Tobias; Sticht, Carsten; Dirks, Wilhelm G.; Reissfelder, Christoph; Pallavi, Prama; Keese, Michael"

作者地址："[Guo, Feng; Kan, Kejia; Li, Lin; Eberhard, Johannes; Reissfelder, Christoph; Pallavi, Prama] Heidelberg Univ, Univ Med Mannheim, Med Fac Mannheim, Dept Surg, D-68167 Mannheim, Germany; [Kan, Kejia; Li, Lin; Pallavi, Prama; Keese, Michael] Heidelberg Univ, Med Fac Mannheim, European Ctr Angioscience ECAS, Mannheim, Germany; [Rueckert, Felix] Diakonissen Krankenhaus Speyer, Surg Dept, D-67346 Speyer, Germany; [Rueckert, Wolfgang] Ingenieurburo Dr Ing Ruckert Data Anal, Ingenieurburo Dr, Kirchweg 4, D-57647 Nistertal, Germany; [May, Tobias] InSCREENeX GmbH, Inhoffenstr 7, D-38124 Braunschweig, Germany; [Sticht, Carsten] Heidelberg Univ, Med Fac Mannheim, Next Generat Sequencing Core Facil, Mannheim, Germany; [Dirks, Wilhelm G.] German Collect Microorg & Cell Cultures GmbH, Leibniz Inst DSMZ, Inhoffenstr 7B, D-38124 Braunschweig, Germany; [Keese, Michael] Theresienkrankenhaus, Dept Vasc Surg, D-68165 Mannheim, Germany; [Guo, Feng] Chongqing Med Univ, Affiliated Hosp 1, Dept Vasc Surg, Chongqing 400016, Peoples R China"

通信作者："Pallavi, P (通讯作者)，Heidelberg Univ, Univ Med Mannheim, Med Fac Mannheim, Dept Surg, D-68167 Mannheim, Germany.; Pallavi, P; Keese, M (通讯作者)，Heidelberg Univ, Med Fac Mannheim, European Ctr Angioscience ECAS, Mannheim, Germany.; Keese, M (通讯作者)，Theresienkrankenhaus, Dept Vasc Surg, D-68165 Mannheim, Germany."

来源：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

ESI学科分类：CHEMISTRY

WOS号：WOS:001060634600001

JCR分区：Q1

影响因子：4.9

年份：2023

卷号：24

期号：17

开始页：　

结束页：　

文献类型：Article

关键词：chemosensitivity; RNA-Seq; patient-tailored therapy; chemotherapy; regression analysis; statistical comparison of populations

摘要："There is an ongoing need for patient-specific chemotherapy for pancreatic cancer. Tumour cells isolated from human tissues can be used to predict patients' response to chemotherapy. However, the isolation and maintenance of pancreatic cancer cells is challenging because these cells become highly vulnerable after losing the tumour microenvironment. Therefore, we investigated whether the cells retained their original characteristics after lentiviral transfection and expansion. Three human primary pancreatic cancer cell lines were lentivirally transduced to create expandable (Ex) cells which were then compared with primary (Pri) cells. No obvious differences in the morphology or epithelial-mesenchymal transition (EMT) were observed between the primary and expandable cell lines. The two expandable cell lines showed higher proliferation rates in the 2D and 3D models. All three expandable cell lines showed attenuated migratory ability. Differences in gene expression between primary and expandable cell lines were then compared using RNA-Seq data. Potential target drugs were predicted by differentially expressed genes (DEGs), and differentially expressed pathways (DEPs) related to tumour-specific characteristics such as proliferation, migration, EMT, drug resistance, and reactive oxygen species (ROS) were investigated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We found that the two expandable cell lines expressed similar chemosensitivity and redox-regulatory capability to gemcitabine and oxaliplatin in the 2D model as compared to their counterparts. In conclusion, we successfully generated expandable primary pancreatic cancer cell lines using lentiviral transduction. These expandable cells not only retain some tumour-specific biological traits of primary cells but also show an ongoing proliferative capacity, thereby yielding sufficient material for drug response assays, which may provide a patient-specific platform for chemotherapy drug screening."

基金机构：Thanks to Carolina de la Torre and Stefanie Uhlig for assessing RNA integrity and sorting cells. Thanks to Manfred Frey for providing Grx1-roGFP3 and Ramkumar Ramani Mohan for isolating the primary MaPac107 cell line.

基金资助正文：Thanks to Carolina de la Torre and Stefanie Uhlig for assessing RNA integrity and sorting cells. Thanks to Manfred Frey for providing Grx1-roGFP3 and Ramkumar Ramani Mohan for isolating the primary MaPac107 cell line.