ArticleThe Journal of biological chemistry2014
Platelet-derived growth factor primes cancer-associated fibroblasts for apoptosis.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Therapy for advanced cholangiocarcinoma: Current knowledge and future potential.Journal of cellular and molecular medicine · 2021Pooled it
- The application of nanotechnology in regulating mitochondrial function in tumor microenvironment for cancer therapy.Theranostics · 2026Review
- Plasma cytokine profiles in oral and oropharyngeal squamous cell carcinoma.BMC oral health · 2025Article
- Cancer-Associated Fibroblasts: Heterogeneity, Cancer Pathogenesis, and Therapeutic Targets.MedComm · 2025Review
- Identification of a novel anoikis-related gene signature to predict prognosis and tumor microenvironment in intrahepatic cholangiocarcinoma carcinoma.Discover oncology · 2025Article
- Lung cancer-associated fibroblasts-mediated collagen deposition drives mediastinal lymph node metastasis in non-small cell lung cancer.Frontiers in oncology · 2025Article
- MiR-3529-3p from PDGF-BB-induced cancer-associated fibroblast-derived exosomes promotes the malignancy of oral squamous cell carcinoma.Discover oncology · 2023Article
- p53 and Myofibroblast Apoptosis in Organ Fibrosis.International journal of molecular sciences · 2023Review
- The Role of Myofibroblasts in Physiological and Pathological Tissue Repair.Cold Spring Harbor perspectives in biology · 2023Review
- Translational Value of Tumor-Associated Lymphangiogenesis in Cholangiocarcinoma.Journal of personalized medicine · 2022Review
- Isolation and characterization of head and neck cancer-derived peritumoral and cancer-associated fibroblasts.Frontiers in oncology · 2022Article
- Cholangiocarcinoma: what are the most valuable therapeutic targets - cancer-associated fibroblasts, immune cells, or beyond T cells?Expert opinion on therapeutic targets · 2021Article
- Extracellular Matrices and Cancer-Associated Fibroblasts: Targets for Cancer Diagnosis and Therapy?Cancers · 2021Review
- PDGF-BB regulates the transformation of fibroblasts into cancer-associated fibroblasts via the lncRNA LURAP1L-AS1/LURAP1L/IKK/IκB/NF-κB signaling pathway.Oncology letters · 2021Article
- Myofibroblast fate plasticity in tissue repair and fibrosis: Deactivation, apoptosis, senescence and reprogramming.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society · 2021Article
- Role of cancer-associated fibroblasts in the resistance to antitumor therapy, and their potential therapeutic mechanisms in non-small cell lung cancer.Oncology letters · 2021Review
- Intrahepatic cholangiocarcinoma: Morpho-molecular pathology, tumor reactive microenvironment, and malignant progression.Advances in cancer research · 2021Review
- Review
- Mitochondria at Center of Exchanges between Cancer Cells and Cancer-Associated Fibroblasts during Tumor Progression.Cancers · 2020Review
- The Emerging Role of PPAR Beta/Delta in Tumor Angiogenesis.PPAR research · 2020Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Desmoplastic malignancies such as cholangiocarcinoma (CCA) are characterized by a dense stroma containing an abundance of myofibroblasts termed cancer-associated fibroblasts (CAF). The CAF phenotype represents an "activated state" in which cells are primed for cell death triggered by BH3 mimetics. Accordingly, this primed state may be therapeutically exploited. To elucidate the mechanisms underlying this poorly understood apoptotic priming, we examined the role of platelet-derived growth factor (PDGF) in CAF priming for cell death given its prominent role in CAF activation. PDGF isomers PDGF-B and PDGF-D are abundantly expressed in CCA cells derived from human specimens. Either isomer sensitizes myofibroblasts to cell death triggered by BH3 mimetics. Similar apoptotic sensitization was observed with co-culture of myofibroblasts and CCA cells. Profiling of Bcl-2 proteins expressed by PDGF-primed myofibroblasts demonstrated an increase in cellular levels of Puma. PDGF-mediated increases in cellular Puma levels induced proapoptotic changes in Bak, which resulted in its binding to Bcl-2. Short hairpin RNA-mediated down-regulation of Puma conferred resistance to PDGF-mediated apoptotic priming. Conversely, the BH3 mimetic navitoclax disrupted Bcl-2/Bak heterodimers, allowing Bak to execute the cell death program. Treatment with a Bcl-2-specific BH3 mimetic, ABT-199, reduced tumor formation and tumor burden in a murine model of cholangiocarcinoma. Collectively, these findings indicate that apoptotic priming of CAF by PDGF occurs via Puma-mediated Bak activation, which can be converted to active full-blown apoptosis by navitoclax or ABT-199 for therapeutic benefit.
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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.