ArticlePloS one2017
Reprogramming Malignant Cancer Cells toward a Benign Phenotype following Exposure to Human Embryonic Stem Cell Microenvironment.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed.
- Pluripotent stem cell-derived extracellular vesicles: Cell type-dependent effect on tumorigenicity in cancer cell lines.Journal of cell communication and signaling · 2026Article
- Cancer Reversion Therapy: Prospects, Progress and Future Directions.Current issues in molecular biology · 2025Review
- Extracellular vesicles as delivery vehicles and therapeutic agents for glioblastoma treatment: A systematic review of in vitro and in vivo preclinical studies.Asian journal of pharmaceutical sciences · 2025Review
- Exosomes in Glioma: Diagnostic and Therapeutic Potentials.Advances in oncology · 2025Article
- miRNAs from Zebrafish Embryo Extracts Inhibit Breast Cancer Invasiveness and Migration by Modulating miR-218-5p/PI3K Pathway.International journal of molecular sciences · 2025Article
- Role of exosomes in transforming growth factor-β-mediated cancer cell plasticity and drug resistance.Exploration of targeted anti-tumor therapy · 2025Review
- Engineered extracellular vesicles derived from pluripotent stem cells: a cell-free approach to regenerative medicine.Burns & trauma · 2025Review
- Blue Light-Induced Mitochondrial Oxidative Damage Underlay Retinal Pigment Epithelial Cell Apoptosis.International journal of molecular sciences · 2024Article
- Review
- The phenotypic reversion of cancer: Experimental evidences on cancer reversibility through epigenetic mechanisms (Review).Oncology reports · 2024Review
- Extracellular Vesicles in Therapeutics: A Comprehensive Review on Applications, Challenges, and Clinical Progress.Pharmaceutics · 2024Review
- Tumor-derived extracellular vesicle drug delivery system for chemo-photothermal-immune combination cancer treatment.iScience · 2024Article
- Emerging role of exosomal microRNA in liver cancer in the era of precision medicine; potential and challenges.Frontiers in molecular biosciences · 2024Review
- Effect of infiltrating immune cells in tumor microenvironment on metastasis of hepatocellular carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2023Review
- Exploring the dynamic interplay between cancer stem cells and the tumor microenvironment: implications for novel therapeutic strategies.Journal of translational medicine · 2023Review
- Connecting the dots: Melanoma cell of origin, tumor cell plasticity, trans-differentiation, and drug resistance.Pigment cell & melanoma research · 2023Review
- Cellular Adaptation Takes Advantage of Atavistic Regression Programs during Carcinogenesis.Cancers · 2023Review
- Review
- Recent Progress in Extracellular Vesicle-Based Carriers for Targeted Drug Delivery in Cancer Therapy.Pharmaceutics · 2023Review
- Human pluripotent stem cell-derived extracellular vesicles: From now to the future.World journal of stem cells · 2023Review
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The embryonic microenvironment is well known to be non-permissive for tumor development because early developmental signals naturally suppress the expression of proto-oncogenes. In an analogous manner, mimicking an early embryonic environment during embryonic stem cell culture has been shown to suppress oncogenic phenotypes of cancer cells. Exosomes derived from human embryonic stem cells harbor substances that mirror the content of the cells of origin and have been reported to reprogram hematopoietic stem/progenitor cells via horizontal transfer of mRNA and proteins. However, the possibility that these embryonic stem cells-derived exosomes might be the main effectors of the anti-tumor effect mediated by the embryonic stem cells has not been explored yet. The present study aims to investigate whether exosomes derived from human embryonic stem cells can reprogram malignant cancer cells to a benign stage and reduce their tumorigenicity. We show that the embryonic stem cell-conditioned medium contains factors that inhibit cancer cell growth and tumorigenicity in vitro and in vivo. Moreover, we demonstrate that exosomes derived from human embryonic stem cells display anti-proliferation and pro-apoptotic effects, and decrease tumor size in a xenograft model. These exosomes are also able to transfer their cargo into target cancer cells, inducing a dose-dependent increase in SOX2, OCT4 and Nanog proteins, leading to a dose-dependent decrease of cancer cell growth and tumorigenicity. This study shows for the first time that human embryonic stem cell-derived exosomes play an important role in the tumor suppressive activity displayed by human embryonic stem cells.
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