The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Pericytes promote endothelial cell survival through induction of autocrine VEGF-A signaling and Bcl-w expression
Open accessAbstract
Endothelial cells (ECs) in blood vessels under formation are stabilized by the recruitment of pericytes, both in normal tissues and during angiogenesis in pathologic situations, including neoplasia. In the tumor vasculature, besides supporting the functionality of blood flow, pericytes protect ECs from antiangiogenic therapies, and have thus been implicated in clinical resistance to vascular targeting drugs. However, the molecular nature of the crosstalk between pericytes and ECs is largely unchartered. Herein, we identified pericyte-induced survival signals in ECs by isolation of vascular fragments derived from tumors that had been genetically or pharmacologically engineered to be either pericyte-rich or pericyte-poor. Pericytes induced the antiapoptotic protein Bcl-w in tumor ECs both in vivo and in vitro, thereby conveying protection from cytotoxic damage. The pericyte-dependent survival signaling in ECs was consequential to enforcement of an autocrine loop involving VEGF-A expression in ECs. Through molecular and functional studies, we delineated a signal transduction pathway in ECs downstream of integrin αv involving activation of NF-κB as the initiating event of the protective crosstalk from pericytes. Our elucidation of pericyte-derived pro-survival signaling in tumor ECs has potentially important implications for clinical development of antiangiogenic drugs, and suggests new therapeutic targets for rational multitargeting of cancer.
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Cites
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Self-citationEscudier, B., Pluzanska, A., Koralewski, P., Ravaud, A., Bracarda, S., Szczylik, C., Chevreau, C., Filipek, M., Melichar, B., Bajetta, E., et al. (2007) · The Lancet · doi:10.1016/s0140-6736(07)61904-7 · Cited by 2,217
Endothelial/Pericyte Interactions
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Cited by
Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges
Fukumura, D., Kloepper, J., Amoozgar, Z., Duda, D. G., & Jain, R. K. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2018.29 · Cited by 2,027
Pericytes of the neurovascular unit: key functions and signaling pathways
Sweeney, M. D., Ayyadurai, S., & Zlokovic, B. V. (2016) · Nature Neuroscience · doi:10.1038/nn.4288 · Cited by 1,125
Kucharzewska, P., Christianson, H. C., Welch, J. E., Svensson, K. J., Fredlund, E., Ringnér, M., Mörgelin, M., Bourseau-Guilmain, E., Bengzon, J., & Belting, M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1220998110 · Cited by 939
Glioblastoma Stem Cells Generate Vascular Pericytes to Support Vessel Function and Tumor Growth
Cheng, L., Huang, Z., Zhou, W., Wu, Q., Donnola, S., Liu, J. K., Fang, X., Sloan, A. E., Mao, Y., Lathia, J. D., et al. (2013) · Cell · doi:10.1016/j.cell.2013.02.021 · Cited by 905
Cerebral Vascular Disease and Neurovascular Injury in Ischemic Stroke
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Metadata
- Authors
- Franco, M., Roswall, P., Cortez, E., Hanahan, D., & Pietras, K.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2011-09-08
- Volume
- 118
- Issue
- 10
- Pages
- 2906-2917
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1989957765
- Cited by
- 310
- References
- 45
- FWCI
- 8.70
- Type
- journal article
- Language
- en
- Open access
- green
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- Franco, M., Roswall, P., Cortez, E., Hanahan, D., & Pietras, K. (2011). Pericytes promote endothelial cell survival through induction of autocrine VEGF-A signaling and Bcl-w expression. Blood. https://doi.org/10.1182/blood-2011-01-331694
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