PXD040492

PXD040492 is an original dataset announced via ProteomeXchange.

Title	Crosstalk with lung fibroblasts shapes the growth and therapeutic response of mesothelioma cells
Description	Mesothelioma is an aggressive cancer of the mesothelial layer associated with an extensive fibrotic response. The latter is in large part mediated by cancer-associated fibroblasts which mediate tumour progression and poor prognosis. However, understanding of the crosstalk between cancer cells and fibroblasts in this disease is mostly lacking. Here, using co-cultures of patient-derived mesothelioma cell lines and lung fibroblasts, we demonstrate that fibroblast activation is a self-propagated process producing a fibrotic extracellular matrix (ECM) and triggering drug resistance in mesothelioma cells. Following characterisation of mesothelioma cells/fibroblasts signalling crosstalk, we identify several FDA-approved targeted therapies as far more potent than standard-of-care Cisplatin/Pemetrexed in ECM-embedded co-culture spheroid models. In particular, the SRC family kinase inhibitor, Saracatinib, extends overall survival well beyond standard-of-care in a mesothelioma genetically-engineered mouse model. In short, we lay the foundation for the rational design of novel therapeutic strategies targeting mesothelioma/fibroblast communication for the treatment of mesothelioma patients.
HostingRepository	PRIDE
AnnounceDate	2024-01-26
AnnouncementXML	Submission_2024-01-26_07:29:32.676.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Madhumeeta Chadha
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-28 02:49:30	ID requested
⏵ 1	2024-01-26 07:29:33	announced

10.1038/s41419-023-06240-x;

Chrisochoidou Y, Roy R, Farahmand P, Gonzalez G, Doig J, Krasny L, Rimmer EF, Willis AE, MacFarlane M, Huang PH, Carragher NO, Munro AF, Murphy DJ, Veselkov K, Seckl MJ, Moffatt MF, Cookson WOC, Pardo OE, Crosstalk with lung fibroblasts shapes the growth and therapeutic response of mesothelioma cells. Cell Death Dis, 14(11):725(2023) [pubmed]

ProteomeXchange project tag: Cancer (B/D-HPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: mesothelioma, cancer associated fibroblast, signalling crosstalk, targeted therapy

Paul Huang
contact affiliation	The Institute of Cancer Reaserach Moecular and Systems Oncology
contact email	paul.huang@icr.ac.uk
lab head
Madhumeeta Chadha
contact affiliation	The Institute of Cancer Research
contact email	madhumeeta.chadha@icr.ac.uk
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/2024/01/PXD040492

PRIDE project URI

• PRIDE
  1. PXD040492
     1. Label: PRIDE project
     2. Name: Crosstalk with lung fibroblasts shapes the growth and therapeutic response of mesothelioma cells