ArticleThe Journal of biological chemistry2016
Cancer Cell-derived Exosomes Induce Mitogen-activated Protein Kinase-dependent Monocyte Survival by Transport of Functional Receptor Tyrosine Kinases.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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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
64 citing papers in PubMed, 92 citations in OpenAlex.
- Glioblastoma Cells Expressing Oncogenic EGFR Release Multiple Extracellular Vesicle Subpopulations Positive or Negative for EGFR.Journal of extracellular biology · 2026Article
- Exosomes in Osteoarthritis: Emerging Roles in Pathogenesis, Diagnosis, and Therapeutic Potential.Current pharmaceutical design · 2026Review
- Immune Modulation in the Tumor Microenvironment: Bifurcation Analysis of Cancer-CTL-Monocyte Dynamics.Bulletin of mathematical biology · 2025Article
- Extracellular vesicles in multiple myeloma: pathogenesis and therapeutic application.The FEBS journal · 2025Review
- Tumor-derived vesicles in immune modulation: focus on signaling pathways.Frontiers in immunology · 2025Review
- Exosomes in Central Nervous System Diseases: A Comprehensive Review of Emerging Research and Clinical Frontiers.Biomolecules · 2024Review
- Differences in Protein Capture by SP3 and SP4 Demonstrate Mechanistic Insights of Proteomics Cleanup Techniques.Journal of proteome research · 2024Article
- Chronic Lymphocytic Leukemia (CLL)-Derived Extracellular Vesicles Educate Endothelial Cells to Become IL-6-Producing, CLL-Supportive Cells.Biomedicines · 2024Article
- Enigmatic exosomal connection in lung cancer drug resistance.Molecular therapy. Nucleic acids · 2024Review
- Role of Exosomes in Cancer and Aptamer-Modified Exosomes as a Promising Platform for Cancer Targeted Therapy.Biological procedures online · 2024Review
- Tumor-derived small extracellular vesicles in cancer invasion and metastasis: molecular mechanisms, and clinical significance.Molecular cancer · 2024Review
- Hitting the target: cell signaling pathways modulation by extracellular vesicles.Extracellular vesicles and circulating nucleic acids · 2024Review
- Exosome-Delivered EGFR Induced by Acidic Bile Salts Regulates Macrophage M2 Polarization to Promote Esophageal Adenocarcinoma Cell Proliferation.OncoTargets and therapy · 2024Article
- Non-small cell lung carcinoma (NSCLC): Implications on molecular pathology and advances in early diagnostics and therapeutics.Genes & diseases · 2023Review
- Recent findings on the impact of ErbB receptors status on prognosis and therapy of head and neck squamous cell carcinoma.Frontiers in medicine · 2023Review
- Exosomes as mediators of tumor immune escape and immunotherapy in hepatocellular carcinoma.Liver research (Beijing, China) · 2022Review
- Emerging strategies in targeting tumor-resident myeloid cells for cancer immunotherapy.Journal of hematology & oncology · 2022Review
- Exosome Carrier Effects; Resistance to Digestion in Phagolysosomes May Assist Transfers to Targeted Cells; II Transfers of miRNAs Are Better Analyzed via Systems Approach as They Do Not Fit Conventional Reductionist Stoichiometric Concepts.International journal of molecular sciences · 2022Review
- Phosphoproteomic Analysis of Breast Cancer-Derived Small Extracellular Vesicles Reveals Disease-Specific Phosphorylated Enzymes.Biomedicines · 2022Article
- Epidermal growth factor/epidermal growth factor receptor signaling blockage inhibits tumor cell-derived exosome uptake by oral squamous cell carcinoma through macropinocytosis.Cancer science · 2022Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor-associated macrophages (TAM) play pivotal roles in cancer initiation and progression. Monocytes, the precursors of TAMs, normally undergo spontaneous apoptosis within 2 days, but can subsist in the inflammatory tumor microenvironment for continuous survival and generation of sufficient TAMs. The mechanisms underlying tumor-driving monocyte survival remain obscure. Here we report that cancer cell-derived exosomes were crucial mediators for monocyte survival in the inflammatory niche. Analysis of the survival-promoting molecules in monocytes revealed that cancer cell-derived exosomes activated Ras and extracellular signal-regulated kinases in the mitogen-activated protein kinase (MAPK) pathway, resulting in the prevention of caspase cleavage. Phosphorylated receptor tyrosine kinases (RTKs), such as phosphorylated epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER-2), were abundantly expressed in cancer cell-derived exosomes. Knock-out of EGFR or/and HER-2, or alternatively, inhibitors against their phosphorylation significantly disturbed the exosome-mediated activation of the MAPK pathway, inhibition of caspase cleavage, and increase in survival rate in monocytes. Moreover, the deprived survival-stimulating activity of exosomes due to null expression of EGFR and HER-2 could be restored by activation of another RTK, insulin receptor. Overall, our study uncovered a mechanism of tumor-associated monocyte survival and demonstrated that cancer cell-derived exosomes can stimulate the MAPK pathway in monocytes through transport of functional RTKs, leading to inactivation of apoptosis-related caspases. This work provides insights into the long sought question on monocyte survival prior to formation of plentiful TAMs in the tumor microenvironment.
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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.