Dataset Information

Development of a multicellular pancreatic tumor microenvironment system using patient-derived tumor cells.

ABSTRACT: The development of drugs to treat cancer is hampered by the inefficiency of translating pre-clinical in vitro monoculture and mouse studies into clinical benefit. There is a critical need to improve the accuracy of evaluating pre-clinical drug efficacy through the development of more physiologically relevant models. In this study, a human triculture 3D in vitro tumor microenvironment system (TMES) was engineered to accurately mimic the tumor microenvironment. The TMES recapitulates tumor hemodynamics and biological transport with co-cultured human microvascular endothelial cells, pancreatic ductal adenocarcinoma, and pancreatic stellate cells. We demonstrate that significant tumor cell transcriptomic changes occur in the TMES that correlate with the in vivo xenograft and patient transcriptome. Treatment with therapeutically relevant doses of chemotherapeutics yields responses paralleling the patients' clinical responses. Thus, this model provides a unique platform to rigorously evaluate novel therapies and is amenable to using patient tumor material directly, with applicability for patient avatars.

SUBMITTER: Gioeli D

PROVIDER: S-EPMC7486791 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Development of a multicellular pancreatic tumor microenvironment system using patient-derived tumor cells.

Gioeli Daniel D Snow Chelsi J CJ Simmers Michael B MB Hoang Stephen A SA Figler Robert A RA Allende J Ashe JA Roller Devin G DG Parsons J Thomas JT Wulfkuhle Julia D JD Petricoin Emanuel F EF Bauer Todd W TW Wamhoff Brian R BR

Lab on a chip 20190301 7

The development of drugs to treat cancer is hampered by the inefficiency of translating pre-clinical in vitro monoculture and mouse studies into clinical benefit. There is a critical need to improve the accuracy of evaluating pre-clinical drug efficacy through the development of more physiologically relevant models. In this study, a human triculture 3D in vitro tumor microenvironment system (TMES) was engineered to accurately mimic the tumor microenvironment. The TMES recapitulates tumor hemodyn ...[more]

PMID: 30839006

Similar Datasets

Project description:BACKGROUND:Patient-derived tumor models are the new standard for pre-clinical drug testing and biomarker discovery. However, the emerging technology of primary pancreatic cancer organoids has not yet been broadly implemented in research, and complex organotypic models using organoids in co-culture with stromal and immune cellular components of the tumor have yet to be established. In this study, our objective was to develop and characterize pancreatic cancer organoids and multi-cell type organotypic co-culture models to demonstrate their applicability to the study of pancreatic cancer. METHODS:We employed organoid culture methods and flow cytometric, cytologic, immunofluorescent and immunohistochemical methods to develop and characterize patient-derived pancreatic cancer organoids and multi-cell type organotypic co-culture models of the tumor microenvironment. RESULTS:We describe the culture and characterization of human pancreatic cancer organoids from resection, ascites and rapid autopsy sources and the derivation of adherent tumor cell monocultures and tumor-associated fibroblasts from these sources. Primary human organoids displayed tumor-like cellular morphology, tissue architecture and polarity in contrast to cell line spheroids, which formed homogenous, non-lumen forming spheres. Importantly, we demonstrate the construction of complex organotypic models of tumor, stromal and immune components of the tumor microenvironment. Activation of myofibroblast-like cancer associated fibroblasts and tumor-dependent lymphocyte infiltration were observed in these models. CONCLUSIONS:These studies provide the first report of novel and disease-relevant 3D in-vitro models representing pancreatic tumor, stromal and immune components using primary organoid co-cultures representative of the tumor-microenvironment. These models promise to facilitate the study of tumor-stroma and tumor-immune interaction and may be valuable for the assessment of immunotherapeutics such as checkpoint inhibitors in the context of T-cell infiltration.

Dataset Information

Development of a multicellular pancreatic tumor microenvironment system using patient-derived tumor cells.

Publications

Development of a multicellular pancreatic tumor microenvironment system using patient-derived tumor cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets