ArticleThe American journal of pathology2005
Rapid vessel regression, protease inhibition, and stromal normalization upon short-term vascular endothelial growth factor receptor 2 inhibition in skin carcinoma heterotransplants.
Article in The American journal of pathology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 37 citations in OpenAlex.
- Mast cells decrease efficacy of anti-angiogenic therapy by secreting matrix-degrading granzyme B.Nature communications · 2017Article
- Sublethal dose of irradiation enhances invasion of malignant glioma cells through p53-MMP 2 pathway in U87MG mouse brain tumor model.Radiation oncology (London, England) · 2015Article
- Targeting the tumor vasculature to enhance T cell activity.Current opinion in immunology · 2015Review
- Neem leaf glycoprotein prophylaxis transduces immune dependent stop signal for tumor angiogenic switch within tumor microenvironment.PloS one · 2014Article
- Interfering with Gal-1-mediated angiogenesis contributes to the pathogenesis of preeclampsia.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- A vascular niche and a VEGF-Nrp1 loop regulate the initiation and stemness of skin tumours.Nature · 2011Article
- Combined blockade of VEGFR-2 and VEGFR-3 inhibits inflammatory lymphangiogenesis in early and middle stages.Investigative ophthalmology & visual science · 2011Article
- Chemopreventative potential of the cruciferous vegetable constituent phenethyl isothiocyanate in a mouse model of prostate cancer.Journal of the National Cancer Institute · 2011Article
- VEGFR2 heterogeneity and response to anti-angiogenic low dose metronomic cyclophosphamide treatment.BMC cancer · 2010Article
- MMP13 as a stromal mediator in controlling persistent angiogenesis in skin carcinoma.Carcinogenesis · 2010Article
- Platelet-derived growth factor-B normalizes micromorphology and vessel function in vascular endothelial growth factor-A-induced squamous cell carcinomas.The American journal of pathology · 2010Article
- Gelatin in situ zymography on fixed, paraffin-embedded tissue: zinc and ethanol fixation preserve enzyme activity.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2010Article
- Development of a fully human anti-PDGFRbeta antibody that suppresses growth of human tumor xenografts and enhances antitumor activity of an anti-VEGFR2 antibody.Neoplasia (New York, N.Y.) · 2009Article
- Angiogenesis in melanoma.Seminars in oncology · 2007Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis, and blockade of VEGF receptor 2 (VEGFR-2), with the monoclonal antibody DC101, inhibits angiogenesis and tumor growth. To examine the short-term effects of DC101, we surface transplanted the squamous cell carcinoma cell line A5-RT3 onto nude mice. After short-term treatment with DC101, we observed rapid reduction in vascularization and reversion of the tumor phenotype. Beginning 24 hours after treatment, VEGFR-2 inhibition resulted in decreased vessel density within the tenascin-c-staining tumor-associated stroma and reduced endothelial cell proliferation. Stromal expression of matrix metalloproteinase-9 and -13 was drastically reduced 96 hours after VEGFR-2 inhibition as detected by in situ hybridization and in situ zymography. Moreover, the morphology of the tumor-stroma border changed from a highly invasive carcinoma to a well-demarcated, premalignant phenotype. The latter was characterized by the appearance of a regular basement membrane in immunostaining and ultrastructural analyses. These findings suggest that VEGFR-2 inhibition by DC101 evokes very rapid reduction of preformed vessels and decreases both stromal protease expression and gelatinolytic activity, resulting in the modulation of the tumor-stroma border zone and reversion of the tumor phenotype. Thus, short-term inhibition of VEGF signaling results in complex stromal alterations with crucial consequences for the tumor phenotype.
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