Distinct roles of VEGFR-1 and VEGFR-2 in the aberrant hematopoiesis associated with elevated levels of VEGF.

Distinct roles of VEGFR-1 and VEGFR-2 in the aberrant hematopoiesis associated with elevated levels of VEGF. Research Abstract Details 

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Distinct roles of VEGFR-1 and VEGFR-2 in the aberrant hematopoiesis associated with elevated levels of VEGF. Abstract Text:

Yuhui Huang,Xiaolan Chen,Mikhail M Dikov,Sergey V Novitskiy,Claudio A Mosse,Li Yang,David P Carbone,

Vascular endothelial growth factor (VEGF), a major factor in tumor-host interactions, plays a critical role in the aberrant hematopoiesis observed in cancer-bearing hosts. To dissect the roles of VEGF receptor (VEGFR)-1 and VEGFR-2 in cancer-associated hematopoiesis in vivo, we selectively stimulated VEGFR-1 and VEGFR-2 by continuous infusion of receptor-specific ligands or selective blockade with VEGF receptor-specific antibodies in mice infused with recombinant VEGF at levels observed in tumor-bearing animals. We found that the effect of VEGF on the accumulation of Gr1(+)CD11b(+) cells is mediated by VEGFR-2, but that the 2 receptors have opposite effects on lymphocyte development. Pathophysiologic levels of VEGF strongly inhibit T-cell development via VEGFR-2, whereas VEGFR-1 signaling decreases this inhibition. VEGFR-1, and not VEGFR-2, signaling is responsible for the observed increase of splenic B cells. Both receptors are capable of inhibiting dendritic cell function. These data suggest that most of observed aberrant hematopoiesis caused by excess tumor-derived VEGF is mediated by VEGFR-2, and VEGFR-1 alone has very limited independent effects but clearly both positively and negatively modulates the effects of VEGFR-2. Our findings suggest that selective blockade of VEGFR-2 rather than of both receptors may optimally overcome the adverse hematologic consequences of elevated VEGF levels found in malignancy.

Distinct roles of VEGFR-1 and VEGFR-2 in the aberrant hematopoiesis associated with elevated levels of VEGF. Publishing Authors By Initials

Y Huang,X Chen,MM Dikov,SV Novitskiy,CA Mosse,L Yang,DP Carbone,

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Distinct roles of VEGFR-1 and VEGFR-2 in the aberrant hematopoiesis associated with elevated levels of VEGF. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Blood

VOLUME: 110

Page Numbers: 624-31

Journal Abbreviation: Blood

ISSN: 0006-4971

DAY: 21

MONTH: 03

YEAR: 2007

Distinct roles of VEGFR-1 and VEGFR-2 in the aberrant hematopoiesis associated with elevated levels of VEGF. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7603509

Distinct roles of VEGFR-1 and VEGFR-2 in the aberrant hematopoiesis associated with elevated levels of VEGF. Keywords Mesh Terms:

KEYWORDS: Vascular Endothelial Growth Factor Recep

MESH TERMS: physiology

Chemical & Substance for Abstract: Distinct roles of VEGFR-1 and VEGFR-2 in the aberrant hematopoiesis associated with elevated levels of VEGF. Information

Substance Name: Vascular Endothelial Growth Factor Recep

Registry Number: EC 2.7.1.112

Grant and Affiliation Information for Distinct roles of VEGFR-1 and VEGFR-2 in the aberrant hematopoiesis associated with elevated levels of VEGF.

AFFILIATION: Department of Cancer Biology, Vanderbilt University, Nashville, TN 37232-6838, USA.

Country: United States

AGENCY: United States NCI

GRANT: R01CA76321

ACRONYM: CA

MEDLINETA: Blood

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