ArticleBreast cancer research : BCR2018
The hypoxic tumor microenvironment in vivo selects the cancer stem cell fate of breast cancer cells.
Article in Breast cancer research : BCR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 117 citations in OpenAlex.
- Breast Cancer Multicellular Spheroid Models-A Tool for Studying Cancer Biology; a Possible Platform for Drug Screening and Personalized Medicine.International journal of molecular sciences · 2026Review
- Non-Cytotoxic Photodynamic Therapy with Talaporfin Sodium Reduces the Expression of CXCR4 and Enhances Chemotherapeutic Efficacy in Undifferentiated Gastric Cancer Cell Line HGC27.Acta histochemica et cytochemica · 2025Article
- Cancer stem cells in meningiomas: novel insights and therapeutic implications.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- PLGA-Nano-Encapsulated Disulfiram Inhibits Cancer Stem Cells and Targets Non-Small Cell Lung Cancer In Vitro and In Vivo.Biomolecules · 2024Article
- Polyamine Anabolism Promotes Chemotherapy-Induced Breast Cancer Stem Cell Enrichment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Tumoroids, a valid preclinical screening platform for monitoring cancer angiogenesis.Stem cell research & therapy · 2024Review
- Migratory Tumor Cells Cooperate with Cancer Associated Fibroblasts in Hormone Receptor-Positive and HER2-Negative Breast Cancer.International journal of molecular sciences · 2024Article
- Tumor microenvironment of cancer stem cells: Perspectives on cancer stem cell targeting.Genes & diseases · 2024Review
- The regulation of microRNAs on chemoresistance in triple-negative breast cancer: a recent update.Epigenomics · 2024Review
- Hypoxia-informed RBE-weighted beam orientation optimization for intensity modulated proton therapy.Medical physics · 2024Article
- Unveiling the mechanisms and challenges of cancer drug resistance.Cell communication and signaling : CCS · 2024Review
- Spatial transcriptomic analysis of tumour with high and low CAIX expression in TNBC tissue samples using GeoMx™ RNA assay.Histology and histopathology · 2024Article
- Hypoxia-induced TGFBI maintains glioma stem cells by stabilizing EphA2.Theranostics · 2024Article
- Research Progress in the Field of Tumor Model Construction Using Bioprinting: A Review.International journal of nanomedicine · 2024Review
- The ER membrane protein complex restricts mitophagy by controlling BNIP3 turnover.The EMBO journal · 2024Article
- Driving electrochemical reactions at the microscale using CMOS microelectrode arrays.Lab on a chip · 2023Article
- Esophageal cancer stem cells reduce hypoxia-induced apoptosis by inhibiting the GRP78-perk-eIF2α-ATF4-CHOP pathwayJournal of gastrointestinal oncology · 2023Article
- Cancer cell plasticity during tumor progression, metastasis and response to therapy.Nature cancer · 2023Review
- 3D Biomimetic Models to Reconstitute Tumor Microenvironment In Vitro: Spheroids, Organoids, and Tumor-on-a-Chip.Advanced healthcare materials · 2023Review
- The ER membrane protein complex governs lysosomal turnover of a mitochondrial tail-anchored protein, BNIP3, to restrict mitophagy.bioRxiv : the preprint server for biology · 2023Article
16 more citing papers are in PubMed but not listed here.
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4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundTumor hypoxia is an independent prognostic factor associated with poor patient survival. Emerging evidence suggests that hypoxia can potentially maintain or enhance the stem cell phenotype of both normal stem cells and cancer cells. However, it remains to be determined whether cell fate is regulated in vivo by the hypoxic tumor microenvironment (TME).
methodsWe established a hypoxia-sensing xenograft model to identify hypoxic tumor cell in vivo primarily using human breast cancer cell lines MDA-MB-231 and MCF7. Hypoxic tumor cells were identified in situ by fluorescence of green fluorescence protein. They were further isolated from xenografts, purified and sorted by flow cytometry for detailed analysis of their stem cell characteristics.
resultsWe have found that hypoxic tumor cells freshly isolated from xenografts contain increased subpopulations of tumor cells with cancer stem cell (CSC)-like characteristics. The CSC characteristics of the hypoxic tumor cells are further enhanced upon re-implantation in vivo, whereas secondary xenografts derived from the non-hypoxic tumor cells remain similar to the primary xenografts. Interestingly, the phenotypes exhibited by the hypoxic tumor cells are stable and remain distinctively different from those of the non-hypoxic tumor cells isolated from the same tumor mass even when they are maintained under the same ambient culture conditions. Mechanistically, the PI3K/AKT pathway is strongly potentiated in the hypoxic tumor cells and is required to maintain the CSC-like phenotype. Importantly, the differential cell fates between hypoxic and non-hypoxic tumor cells are only found in tumor cells isolated from the hypoxic TME in vivo and are not seen in tumor cells treated by hypoxia in vitro alone.
conclusionsThese previously unknown observations suggest that the hypoxic TME may promote malignant progression and therapy resistance by coordinating induction, selection and/or preferential maintenance of the CSC-like phenotype in tumor cells.
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