Unraveling the influence of endothelial cell density on VEGF-A signaling

Napione, Lucia; Pavan, Simona; Veglio, Andrea; Picco, Andrea; Boffetta, G.; Celani, Antonio; Seano, Giorgio; Primo, Luca; Gamba, A.; Bussolino, Federico

doi:10.1182/blood-2011-11-390666

Cited by 31 publications

(30 citation statements)

References 47 publications

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“…The number of RTKs per cell can vary over a wide range. Thus, in one study the EGFR was present in various cell lines in amounts ranging from 10 3 to 10 6 copies per cell while in another study the VEGFR2 was present at about 0.5-1.0 · 10 5 copies per vascular endothelial cell (Imai et al, 1982;Napione et al, 2012). Thus RTKs can be expressed at levels of thousands to hundreds of thousands of copies per cell; this is potentially a useful range in terms of utilizing RTKs for targeted delivery.…”

Section: The Receptor Tyrosine Kinasesmentioning

confidence: 96%

Cellular Uptake and Intracellular Trafficking of Oligonucleotides: Implications for Oligonucleotide Pharmacology

Juliano

Xin

Carver

et al. 2014

Nucleic Acid Therapeutics

110

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One of the major constraints on the therapeutic use of oligonucleotides is inefficient delivery to their sites of action in the cytosol or nucleus. Recently it has become evident that the pathways of cellular uptake and intracellular trafficking of oligonucleotides can strongly influence their pharmacological actions. Here we provide background information on the basic processes of endocytosis and trafficking and then review recent literature on targeted delivery and subcellular trafficking of oligonucleotides in that context. A variety of approaches including molecular scale ligand-oligonucleotide conjugates, ligand-targeted nanocarriers, and the use of small molecules to enhance oligonucleotide effects are discussed.

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Section: The Receptor Tyrosine Kinasesmentioning

confidence: 96%

Cellular Uptake and Intracellular Trafficking of Oligonucleotides: Implications for Oligonucleotide Pharmacology

Juliano

Xin

Carver

et al. 2014

Nucleic Acid Therapeutics

110

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“…Differential expression of certain RTKs is observed in various tissues or disease states including over-expression of HER2 in some forms of breast cancer (102), overexpression of Trk family members in neuronal tissues (103), and enhanced expression of VEGFR2 in vascular endothelial cells (104). The expression of RTKs can vary widely, ranging from 10 3 to 10 6 copies per cell (105,106). The endogenous ligands for RTKs are all relatively large polypeptides and thus are not ideally suited for delivery approaches.…”

Section: Challenges For Nucleic Acid Deliverymentioning

confidence: 99%

The delivery of therapeutic oligonucleotides

2016

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The oligonucleotide therapeutics field has seen remarkable progress over the last few years with the approval of the first antisense drug and with promising developments in late stage clinical trials using siRNA or splice switching oligonucleotides. However, effective delivery of oligonucleotides to their intracellular sites of action remains a major issue. This review will describe the biological basis of oligonucleotide delivery including the nature of various tissue barriers and the mechanisms of cellular uptake and intracellular trafficking of oligonucleotides. It will then examine a variety of current approaches for enhancing the delivery of oligonucleotides. This includes molecular scale targeted ligand-oligonucleotide conjugates, lipid- and polymer-based nanoparticles, antibody conjugates and small molecules that improve oligonucleotide delivery. The merits and liabilities of these approaches will be discussed in the context of the underlying basic biology.

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“…Store-operated Ca 2+ entry (SOCE) is a major Ca 2+ regulatory pathway in non-excitable cells 88 - 90 and, importantly, its molecular components are involved in regulation of Rho-dependent cytoskeletal tension 91 , 92 . Ligand-activated VEGFR recruits phospholipase Cγ (PLCγ), 93 an enzyme that hydrolyzes PtdIns(4,5) P 2 to generate diacylglycerol and inositol-1,4,5-triphosphate (Ins(1,4,5) P 3 ). Increased cytosolic levels of Ins(1,4,5) P 3 stimulate endoplasmic reticulum Ins(1,4,5) P 3 receptors and SOCE 88 .…”

Section: Powering Directional Migration Through Ca2+ Flickersmentioning

confidence: 99%

Integration of signaling and cytoskeletal remodeling by Nck in directional cell migration

Chaki

Rivera

2013

BioArchitecture

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Planar and apical-basal cellular polarization of epithelia and endothelia are crucial during morphogenesis. The establishment of these distinct polarity states and their transitions are regulated by signaling networks that include polarity complexes, Rho GTPases, and phosphoinositides. The spatiotemporal coordination of signaling by these molecules modulates cytoskeletal remodeling and vesicle trafficking to specify membrane domains, a prerequisite for the organization of tissues and organs. Here we present an overview of how activation of the WASp/Arp2/3 pathway of actin remodeling by Nck coordinates directional cell migration and speculate on its role as a signaling integrator in the coordination of cellular processes involved in endothelial cell polarity and vascular lumen formation.

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Unraveling the influence of endothelial cell density on VEGF-A signaling

Cited by 31 publications

References 47 publications

Cellular Uptake and Intracellular Trafficking of Oligonucleotides: Implications for Oligonucleotide Pharmacology

Cellular Uptake and Intracellular Trafficking of Oligonucleotides: Implications for Oligonucleotide Pharmacology

The delivery of therapeutic oligonucleotides

Integration of signaling and cytoskeletal remodeling by Nck in directional cell migration

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