Heterodimers of Placenta Growth Factor/Vascular Endothelial Growth Factor

Cao, Yihai; Chen, Hua; Zhou, Li; Chiang, Ming-Ko; Anand‐Apte, Bela; Weatherbee, James A.; Wang, Yongda; Fang, Faye; Flanagan, John G.; Tsang, Monica

doi:10.1074/jbc.271.6.3154

Cited by 269 publications

(104 citation statements)

References 42 publications

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“…The high affinity binding is to FLT-1, while the lower affinity receptor is yet to be identified (Clauss et al 1996). PlGF/VEGF heterodimers have been found which also bind to the KDR receptor (Cao et al 1996). PlGF and VEGF thus appear capable of acting in unison on both monocytes and endothelial cells (Clauss et al 1996).…”

Section: Introductionmentioning

confidence: 99%

Comparison of expression patterns for placenta growth factor, vascular endothelial growth factor (VEGF), VEGF-B and VEGF-C in the human placenta throughout gestation

Clark

Smith²,

Licence³

et al. 1998

Journal of Endocrinology

192

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Section: Introductionmentioning

confidence: 99%

Comparison of expression patterns for placenta growth factor, vascular endothelial growth factor (VEGF), VEGF-B and VEGF-C in the human placenta throughout gestation

Clark

Smith²,

Licence³

et al. 1998

Journal of Endocrinology

192

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“…a closer homolog of PlGF in its receptor-binding profile (29). Purified heterodimeric VEGF/PlGF has been shown also to bind KDR/Flk-1 (22). The extracellular portion of both receptors consists of seven immunoglobulin (IgG)-like domains, and the receptors share 44% amino acid sequence homology.…”

mentioning

confidence: 99%

“…They also share a number of biochemical and functional features (for a review, see Ref. 20) such that PlGF and VEGF can form heterodimeric molecules in cells in which both genes are expressed (21,22). Alternative splicing of the PlGF primary transcript leads to three forms of the mature human PlGF protein (22)(23)(24).…”

mentioning

confidence: 99%

“…20) such that PlGF and VEGF can form heterodimeric molecules in cells in which both genes are expressed (21,22). Alternative splicing of the PlGF primary transcript leads to three forms of the mature human PlGF protein (22)(23)(24). The two predominant forms, PlGF-1 and PlGF-2 (also known as PlGF-131 and PlGF-152, respectively), differ only by the insertion of a highly basic 21-amino acid stretch at the carboxyl end of the protein.…”

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confidence: 99%

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The Crystal Structure of Human Placenta Growth Factor-1 (PlGF-1), an Angiogenic Protein, at 2.0 Å Resolution

Iyer¹,

Leonidas²,

Swaminathan³

et al. 2001

Journal of Biological Chemistry

100

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The angiogenic molecule placenta growth factor (PlGF) is a member of the cysteine-knot family of growth factors. In this study, a mature isoform of the human PlGF protein, PlGF-1, was crystallized as a homodimer in the crystallographic asymmetric unit, and its crystal structure was elucidated at 2.0 Å resolution. The overall structure of PlGF-1 is similar to that of vascular endothelial growth factor (VEGF) with which it shares 42% amino acid sequence identity. Based on structural and biochemical data, we have mapped several important residues on the PlGF-1 molecule that are involved in recognition of the fms-like tyrosine kinase receptor (Flt-1, also known as VEGFR-1). We propose a model for the association of PlGF-1 and Flt-1 domain 2 with precise shape complementarity, consider the relevance of this assembly for PlGF-1 signal transduction, and provide a structural basis for altered specificity of this molecule.

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“…Placental growth factor (PlGF) is a member of the VEGF family and can form heterodimers with VEGF (4,5). Several splice variants of PlGF exist that bind to VEGFR1/Flt-1 and/or neuropilin-1 (6,7).…”

Section: Introductionmentioning

confidence: 99%

sFLT01: A Novel Fusion Protein with Antiangiogenic Activity

Kurtzberg¹,

Weber²,

Nguyen³

et al. 2011

Molecular Cancer Therapeutics

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AbstractsFLT01 is a novel fusion protein that consists of the VEGF/PlGF (placental growth factor) binding domain of human VEGFR1/Flt-1 (hVEGFR1) fused to the Fc portion of human IgG 1 through a polyglycine linker. It binds to both human VEGF (hVEGF) and human PlGF (hPlGF) and to mouse VEGF (mVEGF) and mouse PlGF (mPlGF). In vitro, sFLT01 inhibited the proliferation of human umbilical vein endothelial cells and pericytes stimulated by either hVEGF or hPlGF. In vivo, sFLT01 had robust and significant antitumor activity in numerous preclinical subcutaneous tumor models including H460 non-small cell lung carcinoma, HT29 colon carcinoma, Karpas 299 lymphoma, MOLM-13 AML (acute myeloid leukemia), 786-O, and RENCA renal cell carcinoma (RCC). sFLT01 also increased median survival in the orthotopic RENCA RCC model. sFLT01 had strong antiangiogenic activity and altered intratumoral microvessel density, blood vessel lumen size and perimeter, and vascular and vessel areas in RCC models. sFLT01 treatment resulted in fewer endothelial cells and pericytes within the tumor microenvironment. sFLT01 in combination with cyclophosphamide resulted in greater inhibition of tumor growth than either agent used alone as a monotherapy in the A673 Ewing's sarcoma model. Gene expression profiling indicated that the molecular changes in the A673 sarcoma tumors are similar to changes observed under hypoxic conditions. sFLT01 is an innovative fusion protein that possessed robust antitumor and antiangiogenic activities in preclinical cancer models. It is a dual targeting agent that neutralizes both VEGF and PlGF and, therefore, has potential as a next generation antiangiogenic therapeutic for oncology. Mol Cancer Ther; 10(3); 404-15. Ó2011 AACR.

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Heterodimers of Placenta Growth Factor/Vascular Endothelial Growth Factor

Cited by 269 publications

References 42 publications

Comparison of expression patterns for placenta growth factor, vascular endothelial growth factor (VEGF), VEGF-B and VEGF-C in the human placenta throughout gestation

Comparison of expression patterns for placenta growth factor, vascular endothelial growth factor (VEGF), VEGF-B and VEGF-C in the human placenta throughout gestation

The Crystal Structure of Human Placenta Growth Factor-1 (PlGF-1), an Angiogenic Protein, at 2.0 Å Resolution

sFLT01: A Novel Fusion Protein with Antiangiogenic Activity

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