ArticleAngiogenesis2011
Neutrophil granulocyte derived MMP-9 is a VEGF independent functional component of the angiogenic switch in pancreatic ductal adenocarcinoma.
Article in Angiogenesis, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 2 of them syntheses that pooled it.
What it found
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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
83 citing papers in PubMed, 2 syntheses or guidelines pooled it, 151 citations in OpenAlex.
- Neutrophil-to-lymphocyte ratio as a predictive biomarker for hyperprogressive disease mediated by immune checkpoint inhibitors: a systematic review and meta-analysis.Frontiers in immunology · 2024Pooled it
- Revealing the prognostic and clinicopathological significance of systemic immune-inflammation index in patients with different stage prostate cancer: A systematic review and meta-analysis.Frontiers in medicine · 2022Pooled it
- Trial
- Neutrophils in cancer.Nature reviews. Cancer · 2026Review
- Heterogeneous evolution of pancreatic cancer microvasculature revealed by longitudinal intravital imaging.Cancer cell international · 2026Article
- The Significance of CXCL1 in Cancer: An Overview of Molecular Mechanisms.International journal of molecular sciences · 2026Review
- Bimodal regulation and precision therapy of neutrophil extracellular traps in liver ischemia-reperfusion injury: recent advances.Frontiers in immunology · 2026Review
- Beyond Structure: The Dynamic Role of the Extracellular Matrix Components in Immune Evasion.Cancer communications (London, England) · 2026Review
- Dynamic Evolution of the Tumor Immune Microenvironment in Malignant Tumors and Emerging Therapeutic Paradigms.MedComm · 2025Review
- Role of Neutrophils in Homeostasis and Diseases.MedComm · 2025Review
- Unveiling the predictive role of systemic inflammation marker in mortality outcomes: a nationwide analysis of cancer survivorship in the United States.Discover oncology · 2025Article
- Tumor microenvironment as niche constructed by cancer stem cells: Breaking the ecosystem to combat cancer.Journal of advanced research · 2025Review
- Inflammation, Immunosuppression, and Immunotherapy in Pancreatic Cancer-Where Are We Now?Cancers · 2025Review
- Impact of systemic immune-inflammation index and its evaluation of optimal threshold in patients with limited-stage small cell lung cancer: a retrospective study based on 572 cases.Translational cancer research · 2025Article
- Interleukin-17A facilitates tumor progressionWorld journal of gastrointestinal oncology · 2025Article
- Immunosuppressive tumor microenvironment in pancreatic cancer: mechanisms and therapeutic targets.Frontiers in immunology · 2025Review
- Targeted anti-cancer therapy: Co-delivery of VEGF siRNA and Phenethyl isothiocyanate (PEITC) via cRGD-modified lipid nanoparticles for enhanced anti-angiogenic efficacy.Asian journal of pharmaceutical sciences · 2024Article
- CT-based radiomics combined with hematologic parameters for survival prediction in locally advanced esophageal cancer patients receiving definitive chemoradiotherapy.Insights into imaging · 2024Article
- Neutrophil extracellular traps in tumor progression of gynecologic cancers.Frontiers in immunology · 2024Review
- Neutrophil Extracellular Traps in Breast Cancer: Roles in Metastasis and Beyond.Journal of Cancer · 2024Review
23 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
Abstract
backgroundVascular endothelial growth factor (VEGF) that is secreted by tumor cells plays a key role in angiogenesis. Matrix metalloproteinase 9 (MMP-9) is produced by inflammatory cells, such as stromal granulocytes (PMN), remodels the extracellular matrix and is known to promote angiogenesis indirectly by interacting with VEGF. The aim of this study was to determine the role of PMN-derived MMP-9, its interaction with VEGF, and the efficacy of anti-angiogenic therapy targeting MMP-9 with oral Doxycycline and VEGF with Bevacizumab in pancreatic cancer (PDAC). METHODOLOGY/PRINCIPAL
findingsInhibitors to MMP-9 (Doxycycline) and VEGF (Bevacizumab) were used alone or in combination in an in vitro angiogenesis assay to test their effect on angiogenesis caused by MMP-9, VEGF, PMN and PDAC cells. In an in vivo model of xenografted PDAC, treatment effects after 14 days under monotherapy with oral Doxycycline or Bevacizumab and a combination of both were evaluated. In vitro, PMN-derived MMP-9 had a direct and strong proangiogenic effect that was independent and additive to PDAC-derived VEGF. Complete inhibition of angiogenesis required the inhibition of VEGF and MMP-9. In vivo, co-localization of MMP-9, PMN and vasculature was observed. MMP inhibition with oral Doxycycline alone resulted in a significant decrease in PDAC growth and mean vascular density comparable to VEGF inhibition alone. CONCLUSIONS/SIGNIFICANCE: PMN derived MMP-9 acts as a potent, direct and VEGF independent angiogenic factor in the context of PDAC. MMP-9 inhibition is as effective as VEGF inhibition. Targeting MMP-9 in addition to VEGF is therefore likely to be important for successful anti-angiogenic treatment in pancreatic cancer.
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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.