ArticleProceedings of the National Academy of Sciences of the United States of America2012
Hypoxia-inducible factor 1-dependent expression of platelet-derived growth factor B promotes lymphatic metastasis of hypoxic breast cancer cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
118 citing papers in PubMed, 2 syntheses or guidelines pooled it, 223 citations in OpenAlex.
- Modulation of tumor-associated lymphangiogenesis by combination immunotherapy approaches in triple-negative breast cancer: a systematic review.Frontiers in immunology · 2026Pooled it
- Association ofJCO global oncology · 2022Pooled it
- Article
- Endothelial von Hippel-Lindau gene deletion causes abnormal blood and lymphatic vasculature through ectopic activation of the HIF-CXCR4 axis.Development (Cambridge, England) · 2026Article
- Transient hypoxia followed by progressive reoxygenation is required for muscle repair.EMBO reports · 2026Article
- The HIF axes in cancer: angiogenesis, metabolism, and immune-modulation.Trends in biochemical sciences · 2025Review
- HIF-1 promotes murine breast cancer brain metastasis by increasing production of integrin β3-containing extracellular vesicles.The Journal of clinical investigation · 2025Article
- Metabolic Effects of Succinate Dehydrogenase Loss in Cancer.Journal of cellular physiology · 2025Review
- Hypoxic Neural Stem Cells Enhance Spinal Cord Repair Through HIF-1a/RAB17-Driven Extracellular Vesicle Release.Journal of extracellular vesicles · 2025Article
- Fibroblast growth factor receptor expression in hemangioblastomas: A novel therapeutic target.PloS one · 2025Article
- Therapeutic Effects of Taurine and Histidine Supplementation in Retinal Diseases.Life (Basel, Switzerland) · 2024Review
- Recent Insights into Roles of Hypoxia-Inducible Factors in Retinal Diseases.International journal of molecular sciences · 2024Review
- Role of microRNA-363 during tumor progression and invasion.Journal of physiology and biochemistry · 2024Review
- Targeting PDGF signaling of cancer-associated fibroblasts blocks feedback activation of HIF-1α and tumor progression of clear cell ovarian cancer.Cell reports. Medicine · 2024Article
- A Molecular Perspective on HIF-1α and Angiogenic Stimulator Networks and Their Role in Solid Tumors: An Update.International journal of molecular sciences · 2024Review
- Hypoxia-induced epigenetic regulation of breast cancer progression and the tumour microenvironment.Frontiers in cell and developmental biology · 2024Review
- Tumour response to hypoxia: understanding the hypoxic tumour microenvironment to improve treatment outcome in solid tumours.Frontiers in oncology · 2024Review
- The role of HIF in angiogenesis, lymphangiogenesis, and tumor microenvironment in urological cancers.Molecular biology reports · 2023Review
- The role of hypoxia on prostate cancer progression and metastasis.Molecular biology reports · 2023Review
- The Progress of Platelets in Breast Cancer.Cancer management and research · 2023Review
58 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lymphatic dissemination from the primary tumor is a major mechanism by which breast cancer cells access the systemic circulation, resulting in distant metastasis and mortality. Numerous studies link activation of hypoxia-inducible factor 1 (HIF-1) with tumor angiogenesis, metastasis, and patient mortality. However, the role of HIF-1 in lymphatic dissemination is poorly understood. In this study, we show that HIF-1 promotes lymphatic metastasis of breast cancer by direct transactivation of the gene encoding platelet-derived growth factor B (PDGF-B), which has proliferative and chemotactic effects on lymphatic endothelial cells. Lymphangiogenesis and lymphatic metastasis in mice bearing human breast cancer orthografts were blocked by administration of the HIF-1 inhibitor digoxin or the tyrosine kinase inhibitor imatinib. Immunohistochemical analysis of human breast cancer biopsies demonstrated colocalization of HIF-1α and PDGF-B, which were correlated with lymphatic vessel area and histological grade. Taken together, these data provide experimental support for breast cancer clinical trials targeting HIF-1 and PDGF-B.
Indexed as
Identifiers
What OpenQuestion holds
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.