Microflow of fluorescently labelled red blood cells in tumours expressing single isoforms of VEGF and their response to vascular targeting agents

Akerman, Simon; Reyes-Aldasoro, Constantino Carlos; Fisher, Mike; Pettyjohn, Katie L.; Björndahl, Meit A.; Evans, Helen; Tozer, Gillian M.

doi:10.1016/j.medengphy.2010.09.006

Cited by 3 publications

(3 citation statements)

References 24 publications

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“…. Preliminary data for RCV effects of CA4P at a single time point (24 hr) after CA4P ± SU5416 have been published as conference proceedings …”

Section: Methodssupporting

confidence: 64%

“…Preliminary data for RCV effects of CA4P at a single time point (24 hr) after CA4P 6 SU5416 have been published as conference proceedings. 35 Statistics A one-way analysis of variance (ANOVA), followed by a Tukey Kramer HSD post-test was used for comparing multiple groups; an unpaired Student's t-test was used for comparing two independent groups; a paired t-test was used for comparing IFP before and after treatment in the same tumor and a two-way ANOVA followed by a Bonferroni post-test was used for analyzing multiple groups with more than one variable (treatment and tumor type) (Prism 5 for Mac OS X). Differences between groups, where time courses were obtained, were analyzed using a mixed-design ANOVA for repeated measures (SPSS version 11.0.2, for the Apple Macintosh, SPSS).…”

Section: Intravital Microscopymentioning

confidence: 99%

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Influence of soluble or matrix-bound isoforms of vascular endothelial growth factor-A on tumor response to vascular-targeted strategies

et al. 2013

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Antiangiogenic therapy based on blocking the actions of vascular endothelial growth factor‐A (VEGF) can lead to “normalization” of blood vessels in both animal and human tumors. Differential expression of VEGF isoforms affects tumor vascular maturity, which could influence the normalization process and response to subsequent treatment. Fibrosarcoma cells expressing only VEGF120 or VEGF188 isoforms were implanted either subcutaneously (s.c.) or in dorsal skin‐fold “window” chambers in SCID mice. VEGF120 was associated with vascular fragility and hemorrhage. Tumor‐bearing mice were treated with repeat doses of SU5416, an indolinone receptor tyrosine kinase inhibitor with activity against VEGFR‐2 and proven preclinical ability to induce tumor vascular normalization. SU5416 reduced vascularization in s.c. implants of both VEGF120 and VEGF188 tumors. However, in the window chamber, SU5416 treatment increased red cell velocity in VEGF120 (representing vascular normalization) but not VEGF188 tumors. SU5416 treatment had no effect on growth or necrosis levels in either tumor type but tended to counteract the increase in interstitial fluid pressure seen with growth of VEGF120 tumors. SU5416 pretreatment resulted in the normally fragile blood vessels in VEGF120‐expressing tumors becoming resistant to the vascular damaging effects of the tubulin‐binding vascular disrupting agent (VDA), combretastatin A4 3‐O‐phosphate (CA4P). Thus, vascular normalization induced by antiangiogenic treatment can reduce the efficacy of subsequent VDA treatment. Expression of VEGF120 made tumors particularly susceptible to vascular normalization by SU5416, which in turn made them resistant to CA4P. Therefore, VEGF isoform expression may be useful for predicting response to both antiangiogenic and vascular‐disrupting therapy.

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“…. Preliminary data for RCV effects of CA4P at a single time point (24 hr) after CA4P ± SU5416 have been published as conference proceedings …”

Section: Methodssupporting

confidence: 64%

Section: Intravital Microscopymentioning

confidence: 99%

Influence of soluble or matrix-bound isoforms of vascular endothelial growth factor-A on tumor response to vascular-targeted strategies

et al. 2013

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“…An alternate hypothesis proposes that vascular normalization occurs by intussusception (198). Normalization may be more successful in tumors showing signs of vascular disorganization, such as the presence of glomeruloid proliferations, or those that secrete higher levels of VEGF 121 ; for example, VEGFR2 blockade specifically increased blood flow in VEGF 120 -expressing but not VEGF 188 -expressing tumors (206, 214). …”

Section: Vegf Isoform Control Of Vascular Patterningmentioning

confidence: 99%

Extracellular regulation of VEGF: Isoforms, proteolysis, and vascular patterning

Vempati¹,

Popel²,

Gabhann³

2014

Cytokine & Growth Factor Reviews

263

230

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The regulation of vascular endothelial growth factor A (VEGF) is critical to neovascularization in numerous tissues under physiological and pathological conditions. VEGF has multiple isoforms, created by alternative splicing or proteolytic cleavage, and characterized by different receptor-binding and matrix-binding properties. These isoforms are known to give rise to a spectrum of angiogenesis patterns marked by differences in branching, which has functional implications for tissues. In this review, we detail the extensive extracellular regulation of VEGF and the ability of VEGF to dictate the vascular phenotype. We explore the role of VEGF-releasing proteases and soluble carrier molecules on VEGF activity. While proteases such as MMP9 can ‘release’ matrix-bound VEGF and promote angiogenesis, for example as a key step in carcinogenesis, proteases can also suppress VEGF’s angiogenic effects. We explore what dictates pro- or anti-angiogenic behavior. We also seek to understand the phenomenon of VEGF gradient formation. Strong VEGF gradients are thought to be due to decreased rates of diffusion from reversible matrix binding, however theoretical studies show that this scenario cannot give rise to lasting VEGF gradients in vivo. We propose that gradients are formed through degradation of sequestered VEGF. Finally, we review how different aspects of the VEGF signal, such as its concentration, gradient, matrix-binding, and NRP1-binding can differentially affect angiogenesis. We explore how this allows VEGF to regulate the formation of vascular networks across a spectrum of high to low branching densities, and from normal to pathological angiogenesis. A better understanding of the control of angiogenesis is necessary to improve upon limitations of current angiogenic therapies.

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Pharmacological manipulation of blood and lymphatic vascularization in ex vivo–cultured mouse embryos

et al. 2012

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Formation of new blood and lymphatic vessels is involved in many physiological and pathological processes, including organ and tumor growth, cancer cell metastasis, fluid drainage and lymphedema. Therefore, the ability to manipulate vascularization in a mammalian system is of particular interest to researchers. Here we describe a method for pharmacological manipulation of de novo and sprouting blood and lymphatic vascular development in ex vivo-cultured mouse embryos. The described protocol can also be used to evaluate the properties of pharmacological agents in growing mammalian tissues and to manipulate other developmental processes. The whole procedure, from embryo isolation to image quantification, takes 3-5 d, depending on the analysis and age of the embryos.

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Microflow of fluorescently labelled red blood cells in tumours expressing single isoforms of VEGF and their response to vascular targeting agents

Cited by 3 publications

References 24 publications

Influence of soluble or matrix-bound isoforms of vascular endothelial growth factor-A on tumor response to vascular-targeted strategies

Influence of soluble or matrix-bound isoforms of vascular endothelial growth factor-A on tumor response to vascular-targeted strategies

Extracellular regulation of VEGF: Isoforms, proteolysis, and vascular patterning

Pharmacological manipulation of blood and lymphatic vascularization in ex vivo–cultured mouse embryos

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