The DOI matches its Crossref record; 17 of the 17 references it cites were found in a registry or an index.
Endothelial barrier disruption by VEGF-mediated Src activity potentiates tumor cell extravasation and metastasis
Open accessAbstract
VEGF is unique among angiogenic growth factors because it disrupts endothelial barrier function. Therefore, we considered whether this property of VEGF might contribute to tumor cell extravasation and metastasis. To test this, mice lacking the Src family kinases Src or Yes, which maintain endothelial barrier function in the presence of VEGF, were injected intravenously with VEGF-expressing tumor cells. We found a dramatic reduction in tumor cell extravasation in lungs or livers of mice lacking Src or Yes. At the molecular level, VEGF compromises the endothelial barrier by disrupting a VE-cadherin–β-catenin complex in lung endothelium from wild-type, but not Yes-deficient, mice. Disrupting the endothelial barrier directly with anti–VE-cadherin both amplifies metastasis in normal mice and overcomes the genetic resistance in Yes-deficient mice. Pharmacological blockade of VEGF, VEGFR-2, or Src stabilizes endothelial barrier function and suppresses tumor cell extravasation in vivo. Therefore, disrupting Src signaling preserves host endothelial barrier function providing a novel host-targeted approach to control metastatic disease.
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Cites
The biology of VEGF and its receptors
Ferrara, N., Gerber, H.-P., & LeCouter, J. (2003) · Nature Medicine · doi:10.1038/nm0603-669 · Cited by 9,591
Tumor Regression by Targeted Gene Delivery to the Neovasculature
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Self-citationVascular permeability factor (VPF, VEGF) in tumor biology
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Selective Requirement for Src Kinases during VEGF-Induced Angiogenesis and Vascular Permeability
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Self-citationVascular endothelial growth factor induces VE-cadherin tyrosine phosphorylation in endothelial cells
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Self-citationSrc deficiency or blockade of Src activity in mice provides cerebral protection following stroke
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Self-citationOptimization of 4-Phenylamino-3-quinolinecarbonitriles as Potent Inhibitors of Src Kinase Activity
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Cited by
Tumor Metastasis: Molecular Insights and Evolving Paradigms
Valastyan, S., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.09.024 · Cited by 4,011
Metastasis: from dissemination to organ-specific colonization
Nguyen, D. X., Bos, P. D., & Massagué, J. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2622 · Cited by 2,649
Metastatic colonization by circulating tumour cells
Massagué, J., & Obenauf, A. C. (2016) · Nature · doi:10.1038/nature17038 · Cited by 2,062
Mechanisms and regulation of endothelial VEGF receptor signalling
Simons, M., Gordon, E., & Claesson-Welsh, L. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.87 · Cited by 1,498
Real-time imaging reveals the single steps of brain metastasis formation.
Kienast, Y., von Baumgarten, L., Fuhrmann, M., Klinkert, W. E. F., Goldbrunner, R., Herms, J., & Winkler, F. (2010) · Nature Medicine · doi:10.1038/nm.2072 · Cited by 1,138
Metadata
- Authors
- Weis, S., Cui, J., Barnes, L., & Cheresh, D.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2004-10-25
- Volume
- 167
- Issue
- 2
- Pages
- 223-229
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2057711788
- Cited by
- 477
- References
- 17
- FWCI
- 7.98
- Type
- journal article
- Language
- en
- Open access
- bronze
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