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PXD038191-1

PXD038191 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleModelling organ-specific metastatic colonization of cholangiocarcinoma organoids in decellularized lung and lymph nodes
DescriptionCholangiocarcinoma (CCA) is a type of liver cancer with an aggressive phenotype and dismal outcome in patients. Current treatment options are limited, with surgical resection or transplantation the only possibility with curative intent. This becomes unavailable if CCA metastasizes to distant organs, most commonly lung and lymph nodes, which in turn drastically reduces overall survival. Clinically, these metastatic sites have a distinct impact on prognosis and survival, however mechanistic insight is lacking. This is partly due to currently available models that fail to mimic the complexity of tissue-specific environments for metastatic CCA. To create an in vitro model in which interaction between epithelial tumor cells and their surrounding extracellular matrix (ECM) can be studied in a metastatic setting, we combined patient-derived CCA organoids (CCAOs) (n=3) with decellularized human lung (n=3) and decellularized human lymph node (n=13). Decellularization resulted in removal of cells while preserving ECM structure and retaining important characteristics of the tissue origin. This includes a tissue-specific ECM protein signature and macro and micro-scale mechanical properties, which reveal the local heterogeneity of the ECM. After recellularization, gene expression analysis showed metastasis-related processes, including epithelial-to-mesenchymal transition, cancer stem cell plasticity, and ECM production, are significantly influenced by the ECM in an organ-specific manner. Furthermore, we find that CCAOs exhibit significant differences in migration and proliferation dynamics depending on metastatic site, the original patient tumor, and donor of target organ. Thus, CCA metastatic outgrowth is dictated both by the tumor itself as well as by the ECM of the target organ. In conclusion, convergence of CCAOs with its organ-specific location of metastasis, obtained by decellularization, provides a valuable tool for research on metastatic colonization in CCA.
HostingRepositoryPRIDE
AnnounceDate2023-01-11
AnnouncementXMLSubmission_2023-01-11_03:34:47.338.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJeroenDemmers
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-11-17 03:53:40ID requested
12023-01-11 03:34:47announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Metastatic colonization
decellularization
cholangiocarcinoma
tumor organoids;
Contact List
JeroenDemmers
contact affiliationProteomics Center, Erasmus MC
contact emailj.demmers@erasmusmc.nl
lab head
JeroenDemmers
contact affiliationProteomics Center, Erasmus University Medical Center, Rotterdam, The Netherlands
contact emailj.demmers@erasmusmc.nl
dataset submitter
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Dataset FTP location
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