Journal ArticleDOI
Formation of endothelial cell networks.
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TLDR
The authors showed that VEGF can stimulate the elongation, network formation and branching of non-proliferating endothelial cells in culture that are deprived of oxygen and nutrients.Abstract:
The growth factor VEGF (vascular endothelial growth factor) promotes the formation of blood vessels in a process known as angiogenesis by inducing the proliferation and migration of endothelial cells1. We show here that VEGF has another proangiogenic function — it can stimulate the elongation, network formation and branching of non-proliferating endothelial cells in culture that are deprived of oxygen and nutrients. As endothelial cells in tumours are exposed to chronic or intermittent hypoxic conditions2,3, we propose that autocrine endothelial VEGF contributes to the formation of blood vessels in a tumour and promotes its survival.read more
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Processing of VEGF-A by matrix metalloproteinases regulates bioavailability and vascular patterning in tumors
Abstract: Vascular endothelial growth factor (VEGF) is a critical mediator of blood vessel formation during development and in pathological conditions. In this study, we demonstrate that VEGF bioavailability is regulated extracellularly by matrix metalloproteinases (MMPs) through intramolecular processing. Specifically, we show that a subset of MMPs can cleave matrix-bound isoforms of VEGF, releasing soluble fragments. We have mapped the region of MMP processing, have generated recombinant forms that mimic MMP-cleaved and MMP-resistant VEGF, and have explored their biological impact in tumors. Although all forms induced similar VEGF receptor 2 phosphorylation levels, the angiogenic outcomes were distinct. MMP-cleaved VEGF promoted the capillary dilation of existent vessels but mediated a marginal neovascular response within the tumor. In contrast, MMP-resistant VEGF supported extensive growth of thin vessels with multiple and frequent branch points. Our findings support the view that matrix-bound VEGF and nontethered VEGF provide different signaling outcomes. These findings reveal a novel aspect in the regulation of extracellular VEGF that holds significance for vascular patterning.
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Isolation and Characterization of Dermal Lymphatic and Blood Endothelial Cells Reveal Stable and Functionally Specialized Cell Lineages
Ernst Kriehuber,Silvana Breiteneder-Geleff,Marion Groeger,Afschin Soleiman,Sebastian F. Schoppmann,Georg Stingl,Dontscho Kerjaschki,Dieter Maurer +7 more
TL;DR: LECs and BECs constitute stable and specialized EC lineages equipped with the potential to navigate leukocytes and, perhaps also, tumor cells into and out of the tissues.
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Loss of HIF-1α in endothelial cells disrupts a hypoxia-driven VEGF autocrine loop necessary for tumorigenesis
Nan Tang,Lianchun Wang,Jeffrey D. Esko,Frank J. Giordano,Yan Huang,Hans-Peter Gerber,Napoleone Ferrara,Randall S. Johnson +7 more
TL;DR: It is found that loss of HIF-1alpha inhibits a number of important parameters of EC behavior during angiogenesis: these include proliferation, chemotaxis, extracellular matrix penetration, and wound healing.
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Oxygen Gradients in the Microcirculation
TL;DR: Oxygen gradients measured in the arteriolar wall provide evidence that this structure in vivo is a very large oxygen sink, and suggests a rate of oxygen consumption two orders of magnitude greater than seen in in vitro studies.
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The Role of Angiogenesis in Cancer Treatment.
Mehdi Rajabi,Shaker A. Mousa +1 more
TL;DR: Combinations of anti-angiogenic drugs and other anticancer strategies such as chemotherapy appear essential for optimal outcome in cancer patients.
References
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Journal ArticleDOI
The biology of vascular endothelial growth factor
TL;DR: The establishment of a vascular supply is required for organ development and differentiation as well as for tissue repair and reproductive functions in the adult.
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Mechanisms of angiogenesis and arteriogenesis.
TL;DR: The cellular and molecular mechanisms underlying the formation of endothelium-lined channels and their maturation via recruitment of smooth muscle cells (arteriogenesis) during physiological and pathological conditions are summarized, alongside with possible therapeutic applications.
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Interstitial pH and pO2 gradients in solid tumors in vivo: high-resolution measurements reveal a lack of correlation.
TL;DR: The first combined, high-resolution measurements of interstitial pH and pO2 profiles between adjacent vessels in a human tumor xenograft are reported, using fluorescence ratio imaging and phosphorescence quenching microscopy.
Journal ArticleDOI
Hypoxia Induces Vascular Endothelial Growth Factor in Cultured Human Endothelial Cells
Atsushi Namiki,Edi Brogi,Marianne Kearney,Elizabeth A. Kim,Tiangen Wu,Thierry Couffinhal,Lyuba Varticovski,Jeffrey M. Isner +7 more
TL;DR: The findings establish the potential for an autocrine pathway that may augment and/or amplify the paracrine effects of VEGF in stimulating angiogenesis and demonstrate evidence of receptor autophosphorylation in hypoxic but not normoxic HUVECs.
Journal Article
Fluctuations in red cell flux in tumor microvessels can lead to transient hypoxia and reoxygenation in tumor parenchyma.
Hiroyuki Kimura,Rod D. Braun,Edgardo T. Ong,Richard Hsu,Timothy W. Secomb,Demetrios Papahadjopoulos,Keelung Hong,Mark W. Dewhirst +7 more
TL;DR: Simulations of oxygen transport in a well-vascularized region of a tumor demonstrated that two-fold variations in RCF can produce IH in 30% of the tissue in that region, suggesting that IH is a relatively common phenomenon.