Angiopoietins in angiogenesis and beyond

Tsigkos, Stelios; Koutsilieris, Micheal; Papapetropoulos, Andreas

doi:10.1517/13543784.12.6.933

Cited by 110 publications

(61 citation statements)

References 69 publications

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“…Ang-1 does not induce endothelial cell proliferation directly [50], but acts as a survival factor for endothelial cells [51], induces vessel stabilization [52], tubule formation [53] and plays a key role in mediating interactions between endothelial and matrix cells [54]. Ang-1 is also produced by mast cells in the microenvironment that promotes plasma cell growth and stimulates angiogenesis together with tumor-derived VEGF [59].…”

Section: Angiopoietinsmentioning

confidence: 99%

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Angiogenesis and Multiple Myeloma

Giuliani

Storti

Bolzoni

et al. 2011

Cancer Microenvironment

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The bone marrow microenvironment in multiple myeloma is characterized by an increased microvessel density. The production of pro-angiogenic molecules is increased and the production of angiogenic inhibitors is suppressed, leading to an "angiogenic switch". Here we present an overview of the role of angiogenesis in multiple myeloma, the pro-angiogenic factors produced by myeloma cells and the microenvironment, and the mechanisms involved in the myeloma-induced angiogenic switch. Current data suggest that the increased bone marrow angiogenesis in multiple myeloma is due to the aberrant expression of angiogenic factors by myeloma cells, the subsequent increase in pro-angiogenic activity of normal plasma cells as a result of myeloma cell angiogenic activity, and the increased number of plasma cells overall. Hypoxia also contributes to the angiogenic properties of the myeloma marrow microenvironment. The transcription factor hypoxia-inducible factor-1α is overexpressed by myeloma cells and affects their transcriptional and angiogenic profiles. In addition, potential roles of the tumor suppressor gene inhibitor of growth family member 4 and homeobox B7 have also been recently highlighted as repressors of angiogenesis and pro-angiogenic related genes, respectively. This complex pathogenetic model of myeloma-induced angiogenesis suggests that several proangiogenic molecules and related genes in myeloma cells and the microenvironment are potential therapeutic targets.

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Section: Angiopoietinsmentioning

confidence: 99%

“…IL-6 stimulates VEGF and OPN production by myeloma cells [6, 40,54] and may exert a direct, pro-angiogenic effect [92], suggesting that this cytokine is involved both directly and indirectly in MM-induced angiogenesis.…”

Section: Matrix Metalloproteinasesmentioning

confidence: 99%

Angiogenesis and Multiple Myeloma

Giuliani

Storti

Bolzoni

et al. 2011

Cancer Microenvironment

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“…[51][52][53] Both Ang1 and Ang2 are ligands for the Tie-2 receptor. 54 Recent reports have shown a link between Ang2 and inflammation. 55,56 Since sepsis is characterized by vascular leakage, Ang2 has also been implicated in this condition in humans.…”

Section: Angiopoietinmentioning

confidence: 99%

The Role of Angiopoietin 2 in Hyperoxia-Inuduced Acute Lung Injury

Bhandari¹,

Elias²

2007

Cell Cycle

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“…We chose Ang2 as a model target because it is an important mediator of angiogenesis and a biomarker of colon, prostate, and breast cancers (23,24). The monomeric Ang2 used in this experiment is 66 kDa in size, with an isoelectric point of 5.5 (25).…”

Section: Resultsmentioning

confidence: 99%

Quantitative selection and parallel characterization of aptamers

Cho

Nie

et al. 2013

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

115

114

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Aptamers are promising affinity reagents that are potentially well suited for high-throughput discovery, as they are chemically synthesized and discovered via completely in vitro selection processes. Recent advancements in selection, sequencing, and the use of modified bases have improved aptamer quality, but the overall process of aptamer generation remains laborious and low-throughput. This is because binding characterization remains a critical bottleneck, wherein the affinity and specificity of each candidate aptamer are measured individually in a serial manner. To accelerate aptamer discovery, we devised the Quantitative Parallel Aptamer Selection System (QPASS), which integrates microfluidic selection and nextgeneration sequencing with in situ-synthesized aptamer arrays, enabling simultaneous measurement of affinity and specificity for thousands of candidate aptamers in parallel. After using QPASS to select aptamers for the human cancer biomarker angiopoietin-2 (Ang2), we in situ synthesized arrays of the selected sequences and obtained equilibrium dissociation constants (K d ) for every aptamer in parallel. We thereby identified over a dozen high-affinity Ang2 aptamers, with K d as low as 20.5 ± 7.3 nM. The same arrays enabled us to quantify binding specificity for these aptamers in parallel by comparing relative binding of differentially labeled target and nontarget proteins, and by measuring their binding affinity directly in complex samples such as undiluted serum. Finally, we show that QPASS offers a compelling avenue for exploring structure−function relationships for large numbers of aptamers in parallel by coupling array-based affinity measurements with next-generation sequencing data to identify nucleotides and motifs within the aptamer that critically affect Ang2 binding.

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Angiopoietins in angiogenesis and beyond

Cited by 110 publications

References 69 publications

Angiogenesis and Multiple Myeloma

Angiogenesis and Multiple Myeloma

The Role of Angiopoietin 2 in Hyperoxia-Inuduced Acute Lung Injury

Quantitative selection and parallel characterization of aptamers

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