PXD043511-2

PXD043511 is an original dataset announced via ProteomeXchange.

Title	Primary and hTERT-transduced mesothelioma-associated fibroblasts but not primary or hTERT-transduced mesothelial cells stimulate growth of human mesothelioma cells_Secreted proteins
Description	Introduction: Pleural mesothelioma (PM) is known as one of the most aggressive malignancies among all cancers, despite of usually absent tumor-driver mutations in oncogenes. It develops in a unique inflammatory tumor microenvironment (TME), which has been postulated as major contributor of PM’s highly aggressive nature. Mesothelioma-associated fibroblasts (Meso-CAFs), a main component of the TME have recently been shown to substantially stimulate several aspects of PM aggressiveness and promote the malignant transformation of pleural mesothelial cells. However, respective cell models for TME research in PM are still very limited. The most commonly used pleural mesothelial cell line Met5A has been established decades ago and patient-derived Meso-CAFs have just recently been characterized for the first time. The aim of the current study was to generate and characterize pleural mesothelial and Meso-CAF cell models with an extended life span that closely resemble the primary cells isolated from human tissue. Methods: Pleural mesothelial cells and Meso-CAFs were isolated from human tissue of pneumothorax and PM patients, respectively. Retroviral transduction was used to induce stable expression of human telomerase reverse transcriptase (hTERT) and enhanced green fluorescent protein (EGFP) in the primary cells. The established cell models were evaluated by measuring their doubling times, gene expression and protein activity levels of hTERT, as well as the absolute lengths of telomeres. The transduced cells were compared to their primary counterparts on the protein level using proteome analysis and the impact of their conditioned media (CM) on tumor cell growth was investigated by videomicroscopy. Results: All transduced derivatives exhibit elevated hTERT gene expression and protein activity, increased hTERT protein amounts in the nucleus, and moderately higher absolute telomere lengths compared to their parental primary cells. The transduction with hTERT did not elicit marked changes in the morphology of the cells, as well as in their proteomes and secretomes. The CM of primary and hTERT-transduced Meso-CAFs comparably stimulated PM cell growth, while medium conditioned by normal pleural mesothelial cells including their hTERT-transduced derivatives was not able to induce a growth stimulating effect. Conclusion: The hTERT-transduced cells closely resemble their primary counterparts, while retaining telomerase activity, thus preventing replicative senescence. The new cell models provide valuable tools for the investigation of cellular interactions cellular interactions within the TME of PM and thus may help to identify novel biomarkers for early diagnosis and to develop new therapeutic strategies.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:12:37.179.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christopher Gerner
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-03 09:04:52	ID requested
1	2023-10-24 13:55:48	announced
⏵ 2	2023-11-14 09:12:38	announced	2023-11-14: Updated project metadata.
3	2024-10-22 06:13:11	announced	2024-10-22: Updated project metadata.

Ries A, Slany A, Pirker C, Mader JC, Mejri D, Mohr T, Schelch K, Flehberger D, Maach N, Hashim M, Hoda MA, Dome B, Krupitza G, Berger W, Gerner C, Holzmann K, Grusch M, Primary and hTERT-Transduced Mesothelioma-Associated Fibroblasts but Not Primary or hTERT-Transduced Mesothelial Cells Stimulate Growth of Human Mesothelioma Cells. Cells, 12(15):(2023) [pubmed]

submitter keyword: hTERT, mesothelioma-associated fibroblasts, pleural mesothelial cells,Pleural mesothelioma, conditioned medium, human telomerase reverse transcriptase, tumor microenvironment

Christopher Gerner
contact affiliation	University of Vienna, Faculty of Chemistry, Department of Analytical Chemistry
contact email	christopher.gerner@univie.ac.at
lab head
Christopher Gerner
contact affiliation	University of Vienna
contact email	christopher.gerner@univie.ac.at
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043511
     1. Label: PRIDE project
     2. Name: Primary and hTERT-transduced mesothelioma-associated fibroblasts but not primary or hTERT-transduced mesothelial cells stimulate growth of human mesothelioma cells_Secreted proteins