ArticleProceedings of the National Academy of Sciences of the United States of America2016
Intratumoral oxygen gradients mediate sarcoma cell invasion.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed.
- The evolution of cellular therapies in sarcoma: Breakthroughs, challenges, and future directions.Human vaccines & immunotherapeutics · 2026Review
- Immune-stromal interactions at the crossroads of tissue injury, repair, and tumor progression.Med (New York, N.Y.) · 2026Review
- Engineering anisotropic tissues: from structured scaffolds to magnetic actuation.Materials today. Bio · 2026Review
- A Head and Neck Cancer Patient-Specific Microphysiological System for Predicting Response to Chemoradiation.bioRxiv : the preprint server for biology · 2026Article
- Immunometabolism in rheumatoid arthritis: mechanisms, biomarkers, and the path to precision medicine.Frontiers in immunology · 2026Review
- Measuring hypoxia in chronic limb-threatening ischemia usingEJNMMI research · 2025Article
- Hypoxia-responsive nanoparticles for fluorescence diagnosis and therapy of cancer.Theranostics · 2025Review
- Acute Three-Dimensional Hypoxia Regulates Angiogenesis.Advanced healthcare materials · 2025Article
- Oxygen-controllable injectable hydrogel alleviates intervertebral disc degeneration by balancing extracellular matrix metabolism.Materials today. Bio · 2024Article
- Pediatric cancer-pathology and microenvironment influence: a perspective into osteosarcoma and non-osteogenic mesenchymal malignant neoplasms.Discover oncology · 2024Review
- Biophysical interplay between extracellular matrix remodeling and hypoxia signaling in regulating cancer metastasis.Frontiers in cell and developmental biology · 2024Review
- Evaluation of a deuterated triarylmethyl spin probe for in vivo RMagnetic resonance in medicine · 2024Article
- Evaluation of a deuterated triarylmethyl spin probe for in vivobioRxiv : the preprint server for biology · 2023Article
- OScience advances · 2023Article
- Roadmap on biomaterials for women's health.JPhys materials · 2023Article
- Scaffold-mediated switching of lymphoma metabolism in culture.Cancer & metabolism · 2022Article
- Tumor spheroids accelerate persistently invading cancer cells.Scientific reports · 2022Article
- Anti-invasive effects of minoxidil on human breast cancer cells: combination with ranolazine.Clinical & experimental metastasis · 2022Article
- Review
- Osteosarcoma mechanobiology and therapeutic targets.British journal of pharmacology · 2022Review
3 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors.
Funding
Abstract
Hypoxia is a critical factor in the progression and metastasis of many cancers, including soft tissue sarcomas. Frequently, oxygen (O2) gradients develop in tumors as they grow beyond their vascular supply, leading to heterogeneous areas of O2 depletion. Here, we report the impact of hypoxic O2 gradients on sarcoma cell invasion and migration. O2 gradient measurements showed that large sarcoma mouse tumors (>300 mm(3)) contain a severely hypoxic core [≤0.1% partial pressure of O2 (pO2)] whereas smaller tumors possessed hypoxic gradients throughout the tumor mass (0.1-6% pO2). To analyze tumor invasion, we used O2-controllable hydrogels to recreate the physiopathological O2 levels in vitro. Small tumor grafts encapsulated in the hydrogels revealed increased invasion that was both faster and extended over a longer distance in the hypoxic hydrogels compared with nonhypoxic hydrogels. To model the effect of the O2 gradient accurately, we examined individual sarcoma cells embedded in the O2-controllable hydrogel. We observed that hypoxic gradients guide sarcoma cell motility and matrix remodeling through hypoxia-inducible factor-1α (HIF-1α) activation. We further found that in the hypoxic gradient, individual cells migrate more quickly, across longer distances, and in the direction of increasing O2 tension. Treatment with minoxidil, an inhibitor of hypoxia-induced sarcoma metastasis, abrogated cell migration and matrix remodeling in the hypoxic gradient. Overall, we show that O2 acts as a 3D physicotactic agent during sarcoma tumor invasion and propose the O2-controllable hydrogels as a predictive system to study early stages of the metastatic process and therapeutic targets.
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