ArticleHepatology (Baltimore, Md.)2011
Myofibroblast-derived PDGF-BB promotes Hedgehog survival signaling in cholangiocarcinoma cells.
Article in Hepatology (Baltimore, Md.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed, 152 citations in OpenAlex.
- Combined MEK/PD-L1 Inhibition Alters Peripheral Cytokines and Lymphocyte Populations Correlating with Improved Clinical Outcomes in Advanced Biliary Tract Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Cholangiocarcinoma 2026: status quo, unmet needs and priorities.Nature reviews. Gastroenterology & hepatology · 2026Review
- From the invasive front to organotropic pre-metastatic niches: spatial immune regulatory networks governing cholangiocarcinoma dissemination and metastasis-intercepting immunotherapy.Frontiers in immunology · 2026Review
- Combination of oxidative phosphorylation and platelet-derived growth factor inhibitors for the treatment of ovarian cancers.npj women's health · 2026Article
- Therapy-imprinted fibroblast memory in cholangiocarcinoma: rewiring CAF niches for immune evasion and treatment-resistant relapse.Frontiers in immunology · 2026Review
- Molecular Alterations and Pathways in Intrahepatic Cholangiocarcinoma: Available Evidence and New Perspectives.International journal of molecular sciences · 2025Review
- Genetic, Epigenetic, and Microenvironmental Drivers of Cholangiocarcinoma.The American journal of pathology · 2025Review
- Investigating causal relationship among inflammatory cytokines and oropharyngeal cancer: Mendelian randomization.Discover oncology · 2025Article
- The Immune-Genomics of Cholangiocarcinoma: A Biological Footprint to Develop Novel Immunotherapies.Cancers · 2025Review
- Cancer-associated fibroblasts in cholangiocarcinoma: the central nexus of tumor-stroma crosstalk and therapeutic translation.Frontiers in immunology · 2025Review
- Cancer-Associated Fibroblasts Promote Lymphatic Metastasis in Cholangiocarcinoma via the PDGF-BB/PDGFR-β Mediated Paracrine Signaling Network.Aging and disease · 2024Article
- The Tumor Immune Microenvironment plays a Key Role in Driving the Progression of Cholangiocarcinoma.Current cancer drug targets · 2024Review
- Immunohistochemical basis for FAP as a candidate theranostic target across a broad range of cholangiocarcinoma subtypes.Frontiers in nuclear medicine · 2024Article
- Identification of the function ofTranslational cancer research · 2023Article
- Tumor immune microenvironment and the current immunotherapy of cholangiocarcinoma (Review).International journal of oncology · 2023Review
- A Novel Trojan Horse Nanotherapy Strategy Targeting the cPKM-STMN1/TGFB1 Axis for Effective Treatment of Intrahepatic Cholangiocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Recent Updates on Viral Oncogenesis: Available Preventive and Therapeutic Entities.Molecular pharmaceutics · 2023Review
- Angiotensin receptor blockers retard the progression and fibrosis via inhibiting the viability ofClinical and translational medicine · 2023Article
- The role of extracellular vesicles in cholangiocarcinoma tumor microenvironment.Frontiers in pharmacology · 2023Review
- Cancer-Associated Fibroblasts in Cholangiocarcinoma: Current Knowledge and Possible Implications for Therapy.Journal of clinical medicine · 2022Review
34 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
unlabelledCholangiocarcinoma (CCA) cells paradoxically express the death ligand, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and, therefore, are dependent upon potent survival signals to circumvent TRAIL cytotoxicity. CCAs are also highly desmoplastic cancers with a tumor microenvironment rich in myofibroblasts (MFBs). Herein, we examine a role for MFB-derived CCA survival signals. We employed human KMCH-1, KMBC, HuCCT-1, TFK-1, and Mz-ChA-1 CCA cells, as well as human primary hepatic stellate and myofibroblastic LX-2 cells, for these studies. In vivo experiments were conducted using a syngeneic rat orthotopic CCA model. Coculturing CCA cells with myofibroblastic human primary hepatic stellate cells or LX-2 cells significantly decreased TRAIL-induced apoptosis in CCA cells, a cytoprotective effect abrogated by neutralizing platelet-derived growth factor (PDGF)-BB antiserum. Cytoprotection by PDGF-BB was dependent upon Hedgehog (Hh) signaling, because it was abolished by the smoothened (SMO; the transducer of Hh signaling) inhibitor, cyclopamine. PDGF-BB induced cyclic adenosine monophosphate-dependent protein kinase-dependent trafficking of SMO to the plasma membrane, resulting in glioma-associated oncogene (GLI)2 nuclear translocation and activation of a consensus GLI reporter gene-based luciferase assay. A genome-wide messenger RNA expression analysis identified 67 target genes to be commonly up- (50 genes) or down-regulated (17 genes) by both Sonic hedgehog and PDGF-BB in a cyclopamine-dependent manner in CCA cells. Finally, in a rodent CCA in vivo model, cyclopamine administration increased apoptosis in CCA cells, resulting in tumor suppression.
conclusionsMFB-derived PDGF-BB protects CCA cells from TRAIL cytotoxicity by a Hh-signaling-dependent process. These results have therapeutical implications for the treatment of human CCA.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.