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Improved patient-derived tumor models in pancreatic ductal adenocarcinoma employing orthotopic implantation

ABSTRACT: Improved patient-derived tumor models in pancreatic ductal adenocarcinoma employing orthotopic implantation

PROVIDER: PRJNA661474 | ENA |

REPOSITORIES: ENA

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Improved patient-derived tumor models in pancreatic ductal adenocarcinoma employing orthotopic implantation

Project description:Pancreatic ductal adenocarcinoma has a very poor prognosis, and new therapies and preclinical models are urgently needed. We developed patient-derived xenografts (PDXs), established PDX-derived cell lines (PDCLs), and generated cell line-derived xenografts (CDXs), and integrated these to create 13 matched trios, as systematic models for this cancer. Orthotopic implantation (OI) of PDCLs showed tumorigenesis and metastases to the liver and peritoneum. Morphological comparisons of OI-CDX and OI-PDX with passaged tumors showed that histopathological features of the original tumor were maintained in both models. Molecular alterations in PDX tumors (including those to KRAS, TP53, SMAD4, and CDKN2A) were similar to those in the respective PDCLs and CDX tumors. Comparing gene expression in PDCLs, ectopic tumors, and OI tumors, CXCR4 and CXCL12 genes were specifically upregulated in OI tumors, whose immunohistochemical profiles suggested epithelial-mesenchymal transition and adeno-squamous trans-differentiation. These patient-derived tumor models provide useful tools for preclinical research into pancreatic ductal adenocarcinoma. We performed comprehensive gene expression profiling of 13 pancreatic cancer cell lines, 14 CDX and 14 PDX tumors by Affymetrix Gene Chip HG-U133Plus2.0.

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Pulmonary metastasis in xenograft model after orthotopic implantation

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Murine uterus expression profile during Peri-implantation: Pre-implantation vs. Post-implantation

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Plasma miR-181a-5p down-regulation predicts response and improved survival after FOLFIRINOX in pancreatic ductal adenocarcinoma

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