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The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.

Heterozygous Deficiency of PHD2 Restores Tumor Oxygenation and Inhibits Metastasis via Endothelial Normalization

Open access
Mazzone, Massimiliano, Dettori, Daniela, Leite de Oliveira, Rodrigo, Loges, Sonja, Schmidt, Thomas, Jonckx, Bart, Tian, Ya-Min, Lanahan, Anthony A., Pollard, Patrick, Ruiz de Almodovar, Carmen, De Smet, Frederik, Vinckier, Stefan, Aragonés, Julián, Debackere, Koen, Luttun, Aernout, Wyns, Sabine, Jordan, Benedicte, Pisacane, Alberto, Gallez, Bernard, Lampugnani, Maria Grazia, Dejana, Elisabetta, Simons, Michael, Ratcliffe, Peter, Maxwell, Patrick, Carmeliet, Peter·2009·Cell
DOI 10.1016/j.cell.2009.01.020
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Abstract

SUMMARY A key function of blood vessels, to supply oxygen, is impaired in tumors because of abnormalities in their endothelial lining. PHD proteins serve as oxygen sensors and may regulate oxygen delivery. We therefore studied the role of endothelial PHD2 in vessel shaping by implanting tumors in PHD2+/− mice. Haplodeficiency of PHD2 did not affect tumor vessel density or lumen size, but normalized the endothelial lining and vessel maturation. This resulted in improved tumor perfusion and oxygenation and inhibited tumor cell invasion, intravasation, and metastasis. Haplodeficiency of PHD2 redirected the specification of endothelial tip cells to a more quiescent cell type, lacking filopodia and arrayed in a phalanx formation. This transition relied on HIF-driven upregulation of (soluble) VEGFR-1 and VE-cadherin. Thus, decreased activity of an oxygen sensor in hypoxic conditions prompts endothelial cells to readjust their shape and phenotype to restore oxygen supply. Inhibition of PHD2 may offer alternative therapeutic opportunities for anticancer therapy.

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Citations

Cites

Show all 11 references

Research works printed but not linked: 30

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Metadata

Authors
Mazzone, M., Dettori, D., Leite de Oliveira, R., Loges, S., Schmidt, T., Jonckx, B., Tian, Y.-M., Lanahan, A. A., Pollard, P., Ruiz de Almodovar, C., De Smet, F., Vinckier, S., Aragonés, J., Debackere, K., Luttun, A., Wyns, S., Jordan, B., Pisacane, A., Gallez, B., Lampugnani, M. G., Dejana, E., Simons, M., Ratcliffe, P., Maxwell, P., & Carmeliet, P.
Venue
Cell
Publisher
Elsevier BV
Published
2009-03
Volume
136
Issue
5
Pages
839-851
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2009.01.020
OpenAlex
W2136023563
Cited by
812
References
11
FWCI
26.41
Type
journal article
Language
en
Open access
bronze
Licence

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The paper
Mazzone, M., Dettori, D., Leite de Oliveira, R., Loges, S., Schmidt, T., Jonckx, B., Tian, Y.-M., Lanahan, A. A., Pollard, P., Ruiz de Almodovar, C., De Smet, F., Vinckier, S., Aragonés, J., Debackere, K., Luttun, A., Wyns, S., Jordan, B., Pisacane, A., Gallez, B., . . . Carmeliet, P. (2009). Heterozygous Deficiency of PHD2 Restores Tumor Oxygenation and Inhibits Metastasis via Endothelial Normalization. Cell. https://doi.org/10.1016/j.cell.2009.01.020

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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.