The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Processing of VEGF-A by matrix metalloproteinases regulates bioavailability and vascular patterning in tumors
Open accessAbstract
Vascular endothelial growth factor (VEGF) is a critical mediator of blood vessel formation during development and in pathological conditions. In this study, we demonstrate that VEGF bioavailability is regulated extracellularly by matrix metalloproteinases (MMPs) through intramolecular processing. Specifically, we show that a subset of MMPs can cleave matrix-bound isoforms of VEGF, releasing soluble fragments. We have mapped the region of MMP processing, have generated recombinant forms that mimic MMP-cleaved and MMP-resistant VEGF, and have explored their biological impact in tumors. Although all forms induced similar VEGF receptor 2 phosphorylation levels, the angiogenic outcomes were distinct. MMP-cleaved VEGF promoted the capillary dilation of existent vessels but mediated a marginal neovascular response within the tumor. In contrast, MMP-resistant VEGF supported extensive growth of thin vessels with multiple and frequent branch points. Our findings support the view that matrix-bound VEGF and nontethered VEGF provide different signaling outcomes. These findings reveal a novel aspect in the regulation of extracellular VEGF that holds significance for vascular patterning.
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Cites
Coussens, L. M., & Werb, Z. (2002) · Nature · doi:10.1038/nature01322 · Cited by 15,111
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
Angiogenesis in cancer and other diseases
Carmeliet, P., & Jain, R. K. (2000) · Nature · doi:10.1038/35025220 · Cited by 9,070
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Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis
Bergers, G., Brekken, R., McMahon, G., Vu, T. H., Itoh, T., Tamaki, K., Tanzawa, K., Thorpe, P., Itohara, S., Werb, Z., et al. (2000) · Nature Cell Biology · doi:10.1038/35036374 · Cited by 2,797
Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer
Ferrara, N., Hillan, K. J., Gerber, H.-P., & Novotny, W. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1381 · Cited by 2,625
VEGF and the quest for tumour angiogenesis factors
Ferrara, N. (2002) · Nature Reviews Cancer · doi:10.1038/nrc909 · Cited by 1,536
Strategies for MMP inhibition in cancer: innovations for the post-trial era
Overall, C. M., & López-Otín, C. (2002) · Nature Reviews Cancer · doi:10.1038/nrc884 · Cited by 1,349
Houck, K. A., Leung, D. W., Rowland, A. M., Winer, J., & Ferrara, N. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)35712-0 · Cited by 1,127
Cited by
Matrix Metalloproteinases: Regulators of the Tumor Microenvironment
Kessenbrock, K., Plaks, V., & Werb, Z. (2010) · Cell · doi:10.1016/j.cell.2010.03.015 · Cited by 5,151
Remodelling the extracellular matrix in development and disease
Bonnans, C., Chou, J., & Werb, Z. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3904 · Cited by 4,367
VEGF receptor signalling ? in control of vascular function
Olsson, A.-K., Dimberg, A., Kreuger, J., & Claesson-Welsh, L. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1911 · Cited by 3,122
Matrix metalloproteinases and the regulation of tissue remodelling
Page-McCaw, A., Ewald, A. J., & Werb, Z. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2125 · Cited by 2,630
Signal transduction by vascular endothelial growth factor receptors
Koch, S., Tugues, S., Li, X., Gualandi, L., & Claesson-Welsh, L. (2011) · Biochemical Journal · doi:10.1042/bj20110301 · Cited by 1,635
Metadata
- Authors
- Lee, S., Jilani, S. M., Nikolova, G. V., Carpizo, D., & Iruela-Arispe, M. L.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2005-05-23
- Volume
- 169
- Issue
- 4
- Pages
- 681-691
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2030615367
- Cited by
- 703
- References
- 9
- FWCI
- 16.82
- Type
- journal article
- Language
- en
- Open access
- green
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- Lee, S., Jilani, S. M., Nikolova, G. V., Carpizo, D., & Iruela-Arispe, M. L. (2005). Processing of VEGF-A by matrix metalloproteinases regulates bioavailability and vascular patterning in tumors. The Journal of Cell Biology. https://doi.org/10.1083/jcb.200409115
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
