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Heterozygous deficiency of PHD2 restores tumor oxygenation and inhibits metastasis via endothelial normalization.

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Heterozygous deficiency of PHD2 restores tumor oxygenation and inhibits metastasis via endothelial normalization. / Mazzone, Massimiliano; Dettori, Daniela; Rodrigo, Leite de Oliveira; Loges, Sonja; Schmidt, Thomas; Jonckx, Bart; Tian, Ya-Min; Lanahan, Anthony A; Pollard, Patrick; Carmen, Ruiz de Almodovar; Frederik, De Smet; 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.

In: CELL, Vol. 136, No. 5, 5, 2009, p. 839-851.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Mazzone, M, Dettori, D, Rodrigo, LDO, Loges, S, Schmidt, T, Jonckx, B, Tian, Y-M, Lanahan, AA, Pollard, P, Carmen, RDA, Frederik, DS, Vinckier, S, Aragonés, J, Debackere, K, Luttun, A, Wyns, S, Jordan, B, Pisacane, A, Gallez, B, Lampugnani, MG, Dejana, E, Simons, M, Ratcliffe, P, Maxwell, P & Carmeliet, P 2009, 'Heterozygous deficiency of PHD2 restores tumor oxygenation and inhibits metastasis via endothelial normalization.', CELL, vol. 136, no. 5, 5, pp. 839-851. <http://www.ncbi.nlm.nih.gov/pubmed/19217150?dopt=Citation>

APA

Mazzone, M., Dettori, D., Rodrigo, L. D. O., Loges, S., Schmidt, T., Jonckx, B., Tian, Y-M., Lanahan, A. A., Pollard, P., Carmen, R. D. A., Frederik, D. S., 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, 136(5), 839-851. [5]. http://www.ncbi.nlm.nih.gov/pubmed/19217150?dopt=Citation

Vancouver

Mazzone M, Dettori D, Rodrigo LDO, Loges S, Schmidt T, Jonckx B et al. Heterozygous deficiency of PHD2 restores tumor oxygenation and inhibits metastasis via endothelial normalization. CELL. 2009;136(5):839-851. 5.

Bibtex

@article{4be470dd1b2140ebac1c1575e8a51520,
title = "Heterozygous deficiency of PHD2 restores tumor oxygenation and inhibits metastasis via endothelial normalization.",
abstract = "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.",
author = "Massimiliano Mazzone and Daniela Dettori and Rodrigo, {Leite de Oliveira} and Sonja Loges and Thomas Schmidt and Bart Jonckx and Ya-Min Tian and Lanahan, {Anthony A} and Patrick Pollard and Carmen, {Ruiz de Almodovar} and Frederik, {De Smet} and Stefan Vinckier and Juli{\'a}n Aragon{\'e}s and Koen Debackere and Aernout Luttun and Sabine Wyns and Benedicte Jordan and Alberto Pisacane and Bernard Gallez and Lampugnani, {Maria Grazia} and Elisabetta Dejana and Michael Simons and Peter Ratcliffe and Patrick Maxwell and Peter Carmeliet",
year = "2009",
language = "Deutsch",
volume = "136",
pages = "839--851",
journal = "CELL",
issn = "0092-8674",
publisher = "Cell Press",
number = "5",

}

RIS

TY - JOUR

T1 - Heterozygous deficiency of PHD2 restores tumor oxygenation and inhibits metastasis via endothelial normalization.

AU - Mazzone, Massimiliano

AU - Dettori, Daniela

AU - Rodrigo, Leite de Oliveira

AU - Loges, Sonja

AU - Schmidt, Thomas

AU - Jonckx, Bart

AU - Tian, Ya-Min

AU - Lanahan, Anthony A

AU - Pollard, Patrick

AU - Carmen, Ruiz de Almodovar

AU - Frederik, De Smet

AU - Vinckier, Stefan

AU - Aragonés, Julián

AU - Debackere, Koen

AU - Luttun, Aernout

AU - Wyns, Sabine

AU - Jordan, Benedicte

AU - Pisacane, Alberto

AU - Gallez, Bernard

AU - Lampugnani, Maria Grazia

AU - Dejana, Elisabetta

AU - Simons, Michael

AU - Ratcliffe, Peter

AU - Maxwell, Patrick

AU - Carmeliet, Peter

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

M3 - SCORING: Zeitschriftenaufsatz

VL - 136

SP - 839

EP - 851

JO - CELL

JF - CELL

SN - 0092-8674

IS - 5

M1 - 5

ER -