Generation and Characterisation of Novel Pancreatic Adenocarcinoma Xenograft Models and Corresponding Primary Cell Lines

Wennerstrøm, Anna B.; Lothe, Inger Marie Bowitz; Sandhu, Vandana; Kure, Elin H.; Myklebost, Ola; Munthe, Else

doi:10.1371/journal.pone.0103873

Cited by 18 publications

(20 citation statements)

References 31 publications

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“…After we selected “GSE18670” [ 21 ], “GSE15471” [ 22 ], “GSE28735” [ 23 , 24 ] and “GSE58561” [ 25 ] for research, we used the online tool GEO2R provided by the GEO database officially to analyze values of gene expressions. All the microarray data had been normalized using the RMA algorithm.…”

Section: Resultsmentioning

confidence: 99%

Integrated expression profiles analysis reveals novel predictive biomarker in pancreatic ductal adenocarcinoma

Wang

Fang

et al. 2017

Oncotarget

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Pancreatic ductal adenocarcinoma (PDAC) is the most lethal human malignant tumor, with a dismal 5-year survival rate of less than 5%. The lack of specific symptoms at early tumor stages and the paucity of biomarkers contribute to the poor diagnosis of pancreatic ductal adenocarcinoma. To improve prognosis, a screening biomarker for early diagnosis of pancreatic cancer is in urgent need. We searched the databases of expression profiling by array on GEO, aiming at comparing gene expression profile of matched pairs of pancreatic tumor and adjacent non-tumor tissues, and we screen out 4 suitable series of gene expression microarray data (“GSE15471”, “GSE18670”, “GSE28735” and “GSE58561”). After carefully analyzing, 13 DEGs (MYOF, SLC6A6, S100P, HK2, IFI44L, OSBPL3, IGF2BP3, PDK4, IL1R2, ERO1A, EGLN3, PLAC8 and ACSL5) are significantly differentially expressed in four microarray databases in common. After analyzing mRNA expression data and clinical follow-up survey provided in the TCGA database and clinicopathological data of 137 pancreatic ductal adenocarcinoma patients, we carefully demonstrated that three of these differentially expressed genes (ERO1A, OSBPL3 and IFI44L) are correlated with poor prognosis of pancreatic ductal adenocarcinoma patients. In addition, we revealed that cell–matrix adhesion and extracellular matrix were top significantly regulated pathways in pancreatic ductal adenocarcinoma and depicted two protein-protein interactions networks of extracellular matrix related Genes which are dysregulated according to 4 gene expression microarray data mentioned above (“GSE15471”, “GSE18670”, “GSE28735” and “GSE58561”), hoping to shed light on the etiology of PDAC and mechanisms of drug resistance in PDAC in this study.

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Section: Resultsmentioning

confidence: 99%

Integrated expression profiles analysis reveals novel predictive biomarker in pancreatic ductal adenocarcinoma

Wang

Fang

et al. 2017

Oncotarget

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“…The 15% of cases unable to engraft immunodeficient mice have either a low percentage of tumor cells or have a low tumoral mass [ 174 ]. Wennerstrom and coworkers have reported the successful growth of primary pancreatic cancer specimens in NOD/SCID mice IL-2Rγ null (NSG mice) through subcutaneous injection of tumor cells [ 175 ]. The xenotransplanted tumors have been used for the development of new human pancreatic cancer cell lines [ 175 ].…”

Section: Pancreatic Cancer Stem Cellsmentioning

confidence: 99%

Pancreatic Cancer: Molecular Characterization, Clonal Evolution and Cancer Stem Cells

2017

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Pancreatic Ductal Adenocarcinoma (PDAC) is the fourth most common cause of cancer-related death and is the most lethal of common malignancies with a five-year survival rate of <10%. PDAC arises from different types of non-invasive precursor lesions: intraductal papillary mucinous neoplasms, mucinous cystic neoplasms and pancreatic intraepithelial neoplasia. The genetic landscape of PDAC is characterized by the presence of four frequently-mutated genes: KRAS, CDKN2A, TP53 and SMAD4. The development of mouse models of PDAC has greatly contributed to the understanding of the molecular and cellular mechanisms through which driver genes contribute to pancreatic cancer development. Particularly, oncogenic KRAS-driven genetically-engineered mouse models that phenotypically and genetically recapitulate human pancreatic cancer have clarified the mechanisms through which various mutated genes act in neoplasia induction and progression and have led to identifying the possible cellular origin of these neoplasias. Patient-derived xenografts are increasingly used for preclinical studies and for the development of personalized medicine strategies. The studies of the purification and characterization of pancreatic cancer stem cells have suggested that a minority cell population is responsible for initiation and maintenance of pancreatic adenocarcinomas. The study of these cells could contribute to the identification and clinical development of more efficacious drug treatments.

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“…The latest mycoplasma test for all three cell lines was done on 09.02.15. They all tested negative (16). Furthermore, for validation of the results, 127 PDAC samples from the TCGA cohort https://tcgadata.nci.nih.gov/tcga/ were analyzed.…”

Section: Tumor and Matching Normal Samplesmentioning

confidence: 99%

“…The mRNA expression data for the OUH cohort with GEO accession numbers GSE60979 and GSE58561 has been published previously (9,16). The data was background corrected and quantile normalized.…”

Section: Mrna Expression Analysismentioning

confidence: 99%

“…The clinicopathologic characteristics of tumors (excluding three IPMNs and two xenograft cell lines) are presented in Table 1. The clinical data for the cell line is available elsewhere (16). The three IPMNs included in the study represent the benign lesions; hence the clinical features were not presented with malignant adenocarcinomas in Table 1.…”

Section: Clinicopathologic Characteristics Of Periampullary Adenocarcmentioning

confidence: 99%

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The Genomic Landscape of Pancreatic and Periampullary Adenocarcinoma

et al. 2016

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Despite advances in diagnostics, less than 5% of patients with periampullary tumors experience an overall survival of five years or more. Periampullary tumors are neoplasms that arise in the vicinity of the ampulla of Vater, an enlargement of liver and pancreas ducts where they join and enter the small intestine. In this study, we analyzed copy number aberrations using Affymetrix SNP 6.0 arrays in 60 periampullary adenocarcinomas from Oslo University Hospital to identify genome-wide copy number aberrations, putative driver genes, deregulated pathways, and potential prognostic markers. Results were validated in a separate cohort derived from The Cancer Genome Atlas Consortium (n ¼ 127). In contrast to many other solid tumors, periampullary adenocarcinomas exhibited more frequent genomic deletions than gains. Genes in the frequently codeleted region 17p13 and 18q21/22 were associated with cell cycle, apoptosis, and p53 and Wnt signaling. By integrating genomics and transcriptomics data from the same patients, we identified CCNE1 and ERBB2 as candidate driver genes. Morphologic subtypes of periampullary adenocarcinomas (i.e., pancreatobiliary or intestinal) harbor many common genomic aberrations. However, gain of 13q and 3q, and deletions of 5q were found specific to the intestinal subtype. Our study also implicated the use of the PAM50 classifier in identifying a subgroup of patients with a high proliferation rate, which had impaired survival. Furthermore, gain of 18p11 (18p11. 21-23, 18p11.31-32) and 19q13 (19q13.2, 19q13.31-32) and subsequent overexpression of the genes in these loci were associated with impaired survival. Our work identifies potential prognostic markers for periampullary tumors, the genetic characterization of which has lagged.

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Generation and Characterisation of Novel Pancreatic Adenocarcinoma Xenograft Models and Corresponding Primary Cell Lines

Cited by 18 publications

References 31 publications

Integrated expression profiles analysis reveals novel predictive biomarker in pancreatic ductal adenocarcinoma

Integrated expression profiles analysis reveals novel predictive biomarker in pancreatic ductal adenocarcinoma

Pancreatic Cancer: Molecular Characterization, Clonal Evolution and Cancer Stem Cells

The Genomic Landscape of Pancreatic and Periampullary Adenocarcinoma

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