ArticleCancer research2009
VEGF-A induces angiogenesis by perturbing the cathepsin-cysteine protease inhibitor balance in venules, causing basement membrane degradation and mother vessel formation.
Article in Cancer research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.
- Efficacy and safety of biological agents and physical therapies for delayed union or nonunion of fractures: a network meta-analysis of randomized controlled trials.BMC musculoskeletal disorders · 2026Pooled it
- Cystatin C and its Role in the Neuro-Glial-Vascular Unit: Implications for Cerebrovascular Diseases and Neurodegeneration.Neuroscience bulletin · 2026Review
- Cathepsins in prostate cancer: multifunctional regulators in tumor progression and therapeutic prospects-a narrative review.Translational andrology and urology · 2026Review
- Cancer cells metastasize in several types of cancer via two distinct routes, probably based on mechanical signals.Frontiers in cell and developmental biology · 2026Review
- Regulatory roles of non-coding and exosomal RNAs in colorectal cancer: spotlight on angiogenesis.Clinical and experimental medicine · 2025Review
- Sonodynamic Therapy-Based DNA Nanocarriers with Hypoxia-Inducible Factor-1α Silencing Activation for Precision Lung Cancer Therapy.Biomaterials research · 2025Article
- Phenotypic Heterogeneity, Bidirectionality, Universal Cues, Plasticity, Mechanics, and the Tumor Microenvironment Drive Cancer Metastasis.Biomolecules · 2024Review
- Association between various cathepsins and uterine leiomyoma: A Mendelian randomization analysis.PloS one · 2024Article
- Biophysics in tumor growth and progression: from single mechano-sensitive molecules to mechanomedicine.Oncogene · 2023Review
- Serum VEGF levels as a predictor of recurrence in patients with advanced‑stage esophageal squamous cell carcinoma following curative esophagectomy followed by chemotherapy or concurrent radiotherapy.Molecular and clinical oncology · 2023Article
- Dipeptide-Derived Alkynes as Potent and Selective Irreversible Inhibitors of Cysteine Cathepsins.Journal of medicinal chemistry · 2023Article
- Vascularized Tissue Organoids.Bioengineering (Basel, Switzerland) · 2023Review
- The mechanistic immunosuppressive role of the tumour vasculature and potential nanoparticle-mediated therapeutic strategies.Frontiers in immunology · 2022Review
- Dendritic cell vaccine therapy for colorectal cancer.Pharmacological research · 2021Review
- Non-coding RNAs in Regulating Tumor Angiogenesis.Frontiers in cell and developmental biology · 2021Review
- Epigenetic crosstalk between hypoxia and tumor driven by HIF regulation.Journal of experimental & clinical cancer research : CR · 2020Review
- Inhibition of Angiogenesis by Treatment with Cold Atmospheric Plasma as a Promising Therapeutic Approach in Oncology.International journal of molecular sciences · 2020Article
- Relevance of EGFR Between Serum VEGF and MMP-9 in Primary Hepatocellular Carcinoma Patients with Transarterial Chemoembolization.OncoTargets and therapy · 2020Article
- Cathepsin B: A sellsword of cancer progression.Cancer letters · 2019Review
- Axl signaling is an important mediator of tumor angiogenesis.Oncotarget · 2019Article
3 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
12 authors at 4 institutions in 1 country.
Funding
Abstract
Tumors initiate angiogenesis primarily by secreting vascular endothelial growth factor (VEGF-A(164)). The first new vessels to form are greatly enlarged, pericyte-poor sinusoids, called mother vessels (MV), that originate from preexisting venules. We postulated that the venular enlargement necessary to form MV would require a selective degradation of their basement membranes, rigid structures that resist vascular expansion. To identify the specific proteases responsible for MV formation, we induced angiogenesis in mouse tissues with an adenoviral vector expressing VEGF-A(164) (Ad-VEGF-A(164)) or with VEGF-A-secreting TA3/St mammary tumors. We found that MV formation resulted from greatly increased activity of cathepsins (B>S>L) in venules transitioning into MV, as well as from a reciprocal decrease in the expression of several cysteine protease inhibitors (CPI), stefin A and cystatins B and C, by these same venules. Using a fluorescence probe that selectively binds cellular sites of cathepsin protease activity in vivo, we showed that increased cathepsin activity was localized exclusively to perivenular cells, not to venule endothelial cells. CPI strikingly inhibited angiogenesis in the Matrigel assay, and Ad-VEGF-A(164)-induced angiogenesis was reduced by approximately 50% in cathepsin B-null mice. Thus, VEGF-A, whether expressed by interstitial cells infected with an adenoviral vector or by tumor cells, upsets the normal cathepsin-CPI balance in nearby venules, leading to degradation of their basement membranes, an important first step in angiogenesis.
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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.