ArticleStem cells (Dayton, Ohio)2014
Peritoneal milky spots serve as a hypoxic niche and favor gastric cancer stem/progenitor cell peritoneal dissemination through hypoxia-inducible factor 1α.
Article in Stem cells (Dayton, Ohio), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 45 citations in OpenAlex.
- Hypoxia-inducible factors: Regulatory functions and status as a therapeutic target in gastric cancer (Review).Oncology letters · 2026Review
- Metastatic organotropism in peritoneal metastasis: Paget's hypothesis revisited.Clinical and experimental medicine · 2026Review
- Molecular mechanisms of metastatic peritoneal dissemination in gastric adenocarcinoma.Cancer metastasis reviews · 2025Review
- The hypoxia-inducible factor-1α in stemness and resistance to chemotherapy in gastric cancer: Future directions for therapeutic targeting.Frontiers in cell and developmental biology · 2023Review
- Development of the Peritoneal Metastasis: A Review of Back-Grounds, Mechanisms, Treatments and Prospects.Journal of clinical medicine · 2022Review
- Review
- HIF in Gastric Cancer: Regulation and Therapeutic Target.Molecules (Basel, Switzerland) · 2022Review
- Molecular Mechanisms and Potential Rationale of Immunotherapy in Peritoneal Metastasis of Advanced Gastric Cancer.Biomedicines · 2022Review
- Review
- Circulating Tregs Accumulate in Omental Tumors and Acquire Adipose-Resident Features.Cancer immunology research · 2022Article
- Specialized immune responses in the peritoneal cavity and omentum.Journal of leukocyte biology · 2021Review
- Molecular mediators of peritoneal metastasis in pancreatic cancer.Cancer metastasis reviews · 2020Review
- SPHK1-induced autophagy in peritoneal mesothelial cell enhances gastric cancer peritoneal dissemination.Cancer medicine · 2019Article
- Pressurized intraperitoneal aerosol chemotherapy and its effect on gastric-cancer-derived peritoneal metastases: an overview.Clinical & experimental metastasis · 2019Review
- Hypoxia-Induced Phenotypes that Mediate Tumor Heterogeneity.Advances in experimental medicine and biology · 2019Review
- Gastric Cancer Stem Cells: Mechanisms and Therapeutic Approaches.Yonsei medical journal · 2018Review
- The Pattern of Signatures in Gastric Cancer Prognosis.International journal of molecular sciences · 2018Review
- Exosome-mediated peritoneal dissemination in gastric cancer and its clinical applications.Biomedical reports · 2018Review
- Bone morphogenetic protein and activin membrane-bound inhibitor overexpression inhibits gastric tumor cell invasion via the transforming growth factor-β/epithelial-mesenchymal transition signaling pathway.Experimental and therapeutic medicine · 2018Article
- Comprehensive analysis of differentially expressed non-coding RNAs and mRNAs in gastric cancer cells under hypoxic conditions.American journal of translational research · 2018Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Peritoneal dissemination is the most common cause of death in gastric cancer patients. The hypoxic microenvironment plays a major role in controlling the tumor stem cell phenotype and is associated with patients' prognosis through hypoxia-inducible factor-1α (HIF-1α), a key transcriptional factor that responds to hypoxic stimuli. During the peritoneal dissemination process, gastric cancer stem/progenitor cells (GCSPCs) are thought to enter into and maintained in peritoneal milky spots (PMSs), which have hypoxic microenvironments. However, the mechanism through which the hypoxic environment of PMSs regulated GCSPC maintenance is still poorly understood. Here, we investigated whether hypoxic PMSs were an ideal cancer stem cell niche suitable for GCSPC engraftment. We also evaluated the mechanisms through which the HIF-1α-mediated hypoxic microenvironment regulated GCSPC fate. We observed a positive correlation between HIF-1α expression and gastric cancer peritoneal dissemination (GCPD) in gastric cancer patients. Furthermore, the GCSPC population expanded in primary gastric cancer cells under hypoxic condition in vitro, and hypoxic GCSPCs showed enhanced self-renewal ability, but reduced differentiation capacity, mediated by HIF-1α. In an animal model, GCSPCs preferentially resided in the hypoxic zone of PMSs; moreover, when the hypoxic microenvironment in PMSs was destroyed, GCPD was significantly alleviated. In conclusion, our results demonstrated that PMSs served as a hypoxic niche and favored GCSPCs peritoneal dissemination through HIF-1α both in vitro and in vivo. These results provided new insights into the GCPD process and may lead to advancements in the clinical treatment of gastric cancer.
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