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TWEAK/Fn14 signalling promotes cholangiocarcinoma niche formation and progression

ABSTRACT: Cholangiocarcinoma is a cancer of the hepatic bile ducts that is typically detected at a stage too advanced for resection. Additionally, chemotherapy is of limited efficacy, hence, novel therapeutic approaches are urgently required, including targeting of the cancer stroma. A macrophage-derived signal, tumour necrosis factor-like weak inducer of apoptosis (TWEAK), binds to cell-surface fibroblast growth factor-inducible 14 (Fn14), on cholangiocarcinoma cells to induce cytokine and chemokine expression and secretion. These TWEAK-inducible factors from cholangiocarcinoma cells can also affect macrophage polarisation. We characterised proteins secreted by four well-characterised human cholangiocarcinoma cell lines in the presence or absence of recombinant human TWEAK (100 ng/ml), to discover novel TWEAK-inducible factors that could drive pro-tumour niche formation.

INSTRUMENT(S): micrOTOF-Q II

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Prof.Stuart Forbes

PROVIDER: MSV000084273 | MassIVE |

SECONDARY ACCESSION(S): PXD015317

REPOSITORIES: MassIVE

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TWEAK/Fn14 signalling promotes cholangiocarcinoma niche formation and progression.

Dwyer Benjamin J BJ Jarman Edward J EJ Gogoi-Tiwari Jully J Ferreira-Gonzalez Sofia S Boulter Luke L Guest Rachel V RV Kendall Timothy J TJ Kurian Dominic D Kilpatrick Alastair M AM Robson Andrew J AJ O'Duibhir Eoghan E Man Tak Yung TY Campana Lara L Starkey Lewis Philip J PJ Wigmore Stephen J SJ Olynyk John K JK Ramm Grant A GA Tirnitz-Parker Janina E E JEE Forbes Stuart J SJ

Journal of hepatology 20201119 4

<h4>Background & aims</h4>Cholangiocarcinoma (CCA) is a cancer of the hepatic bile ducts that is rarely resectable and is associated with poor prognosis. Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) is known to signal via its receptor fibroblast growth factor-inducible 14 (Fn14) and induce cholangiocyte and myofibroblast proliferation in liver injury. We aimed to characterise its role in CCA.<h4>Methods</h4>The expression of the TWEAK ligand and Fn14 receptor was assessed immuno ...[more]

PMID: 33221352

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