The Original Pathologische Anatomie Leiden-Endothelium Monoclonal Antibody Recognizes a Vascular Endothelial Growth Factor–Binding Site within Neuropilin-1

Jaalouk, Diana E.; Ozawa, Michael G.; Sun, Jessica; Lahdenranta, Johanna; Schlingemann, Reinier O.; Pasqualini, Renata; Arap, Wadih

doi:10.1158/0008-5472.can-07-2737

Cited by 15 publications

(12 citation statements)

References 35 publications

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“…Furthermore, the argument of Jaalouk et al, 4 claiming that anti-PV-1 and PAL-E antibodies cannot recognize the same molecule as they fail to inhibit each other in competitive staining experiments, is invalidated by the fact that all glycoproteins carry multiple antigenic epitopes.…”

Section: Resultsmentioning

confidence: 99%

“…Despite its widespread use, the identification of the PAL-E antigen has proven difficult, and there has been marked confusion regarding the identity of the molecule recognized by PAL-E. [2][3][4] We identified the molecular target of PAL-E as plasmalemma vesicleassociated protein-1 (PV-1). 3,5 Recently, this was challenged by reporting neuropilin-1 (NRP-1) as the antigen for PAL-E. 4 PV-1 is a heavily glycosylated approximately 55-to 65-kDa glycoprotein originally discovered in rat lung endothelium and subsequently found in stomatal diaphragms of endothelial caveolae and transendothelial channels.…”

Section: Introductionmentioning

confidence: 99%

“…3,5 Recently, this was challenged by reporting neuropilin-1 (NRP-1) as the antigen for PAL-E. 4 PV-1 is a heavily glycosylated approximately 55-to 65-kDa glycoprotein originally discovered in rat lung endothelium and subsequently found in stomatal diaphragms of endothelial caveolae and transendothelial channels. 6 NRP-1, on the other hand, was first found as a semaphorin receptor and neuronal cell guidance molecule 7 and later also shown to function during angiogenesis as a VEGFR-2 coreceptor binding VEGF-A 165 .…”

Section: Introductionmentioning

confidence: 99%

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PV-1 is recognized by the PAL-E antibody and forms complexes with NRP-1

Keuschnigg

Tvorogov

Elima

et al. 2012

Blood

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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PV-1 is recognized by the PAL-E antibody and forms complexes with NRP-1

Keuschnigg

Tvorogov

Elima

et al. 2012

Blood

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“…13–15 Recently, this PAL-E antibody was reported to recognize the antigen neuropilin-1 (NRP-1) in human endothelial cells, a vascular endothelial growth factor (VEGF) receptor. 16 …”

Section: Introductionmentioning

confidence: 99%

Maturation of the Fetal Human Choriocapillaris

Baba

Grebe

Hasegawa

et al. 2009

Invest. Ophthalmol. Vis. Sci.

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Purpose The purpose of this study was to examine the structural and functional maturation of the choriocapillaris (CC). We sought to determine when fenestrations formed, pericytes invest the capillaries and endothelial cells became functional. Methods Immunohistochemistry was performed on cryopreserved sections of embryonic/fetal human eyes from 7 to 22 weeks gestation (WG) using antibodies against PAL-E, PV-1 (fenestrations), carbonic anhydrase IV (CA IV), eNOS, and alpha smooth muscle actin (αSMA) and NG2 (two pericyte markers) and endothelial cell (EC) markers (CD34, CD31). Alkaline phosphatase (APase) enzymatic activity was demonstrated by enzyme histochemistry. Transmission electron microscopy (TEM) was performed on 11, 14, 16 and 22 WG eyes. Adult human eyes were used as positive controls. Results All EC markers were present in CC by 7 WG. PAL-E, CA IV and eNOS immunoreactivities and APase activity were present in CC by 7–9 WG. TEM analysis demonstrated how structurally immature this vasculature was even at 11 WG: no basement membrane, absence of pericytes, and poorly formed lumens that were filled with filopodia. The few fenestrations that were observed were often present within the luminal space in the filopodia. Contiguous fenestrations and significant PV-1 were not observed until 21–22 WG. αSMA was prominent at 22 WG and the maturation of pericytes was confirmed by TEM. Conclusions It appears that EC and their precursors have several mature functional characteristics well before they are structurally mature. Although EC make tight junctions early in development, contiguous fenestrations and mature pericytes occur much later in development.

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“…We previously expanded this epitope mapping approach to show that selection of random peptide libraries on the repertoire of circulating immunoglobulins from cancer patients (18,19) can identify immunogenic tumor antigens as molecular targets (20). Moreover, we and other investigators applied similar methodology to therapeutic (21)(22)(23) or diagnostic (24) antibodies in a strategy that could reveal mechanisms of action (22), identify biological reagents for immunization (23), or discover as yet unrecognized antigens (24).…”

Section: Resultsmentioning

confidence: 99%

From combinatorial peptide selection to drug prototype (II): Targeting the epidermal growth factor receptor pathway

Cardó-Vila

Giordano

Sidman

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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The epidermal growth factor receptor (EGFR), a tyrosine kinase, is central to human tumorigenesis. Typically, three classes of drugs inhibit tyrosine kinase pathways: blocking antibodies, small kinase inhibitors, and soluble ligand receptor traps/decoys. Only the first two types of EGFR-binding inhibitory drugs are clinically available; notably, no EGFR decoy has yet been developed. Here we identify small molecules mimicking EGFR and that functionally behave as soluble decoys for EGF and TGFα, ligands that would otherwise activate downstream signaling. After combinatorial library selection on EGFR ligands, a panel of binding peptides was narrowed by structure-function analysis. The most active motif was CVRAC (EGFR 283-287), which is necessary and sufficient for specific EGFR ligand binding. Finally, a synthetic retro-inverted derivative, D (CARVC), became our preclinical prototype of choice. This study reveals an EGFR-decoy drug candidate with translational potential.T he epidermal growth factor receptor (EGFR) is a member of the ErbB family of tyrosine kinase receptors (1, 2). Several lines of evidence indicate that the EGFR is abnormally activated in many types of epithelial tumors. The first therapeutic agent targeted to the EGFR is a monoclonal antibody, cetuximab, which blocks ligand binding and thus inhibits tyrosine kinase activity (3). In the past few years, it has become clear that specific somatic EGFR mutations present in non-small-cell lung cancer potentiate responses to certain low molecular weight tyrosine kinase inhibitors and monoclonal antibodies (1, 4-8); mutation of the K-ras gene also has been associated with survival in patients with advanced colon cancer treated with cetuximab (9). These agents, both antibodies and tyrosine kinase inhibitors, prevent ligand-induced receptor activation and downstream signaling and result in cell cycle arrest, promotion of apoptosis, and inhibition of angiogenesis (10, 11).There are three general classes of agents that inhibit tyrosine kinase receptors: blocking antibodies, small kinase inhibitors, and soluble ligand traps or receptor decoys. However, only agents belonging to the first two classes are currently available for therapeutic intervention: monoclonal antibodies directed at the ligand-binding extracellular domain of the receptor (e.g., cetuximab, panitumumab, zalutumumab, nimotuzumab, and matuzumab) and low-molecular-weight inhibitors of intracellular tyrosine kinase activity (e.g., gefitinib, erlotinib, and lapatinib). Extensive research has recently been done to find EGFR molecular decoys such as Argos, an antagonist of EGFR signaling that was identified in Drosophila (12, 13), or a recombinant form of the extracellular domain of ErbB4 that antagonizes ligand-induced receptor tyrosine phosphorylation (14). Because the EGFR is a central target in oncology, and given the success of this approach with other important ligand-receptor tyrosine kinases such as the vascular endothelial growth factor (VEGF) receptors (15, 16), we reasoned that the combin...

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The Original Pathologische Anatomie Leiden-Endothelium Monoclonal Antibody Recognizes a Vascular Endothelial Growth Factor–Binding Site within Neuropilin-1

Cited by 15 publications

References 35 publications

PV-1 is recognized by the PAL-E antibody and forms complexes with NRP-1

PV-1 is recognized by the PAL-E antibody and forms complexes with NRP-1

Maturation of the Fetal Human Choriocapillaris

From combinatorial peptide selection to drug prototype (II): Targeting the epidermal growth factor receptor pathway

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