PXD038191-1

PXD038191 is an original dataset announced via ProteomeXchange.

Title	Modelling organ-specific metastatic colonization of cholangiocarcinoma organoids in decellularized lung and lymph nodes
Description	Cholangiocarcinoma (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.
HostingRepository	PRIDE
AnnounceDate	2023-01-11
AnnouncementXML	Submission_2023-01-11_03:34:47.338.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	JeroenDemmers
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-11-17 03:53:40	ID requested
⏵ 1	2023-01-11 03:34:47	announced

Dataset with its publication pending

submitter keyword: Metastatic colonization

decellularization

cholangiocarcinoma

tumor organoids;

JeroenDemmers
contact affiliation	Proteomics Center, Erasmus MC
contact email	j.demmers@erasmusmc.nl
lab head
JeroenDemmers
contact affiliation	Proteomics Center, Erasmus University Medical Center, Rotterdam, The Netherlands
contact email	j.demmers@erasmusmc.nl
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/01/PXD038191

PRIDE project URI

• PRIDE
  1. PXD038191
     1. Label: PRIDE project
     2. Name: Modelling organ-specific metastatic colonization of cholangiocarcinoma organoids in decellularized lung and lymph nodes