Lack of ecto-5′-nucleotidase (CD73) promotes arteriogenesis

Böring, Yang Chul; Flögel, Ulrich; Jacoby, Christoph; Heil, Matthias; Schäper, Wolfgang; Schrader, Jürgen

doi:10.1093/cvr/cvs286

Cited by 21 publications

(15 citation statements)

References 53 publications

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“…These results support that tumor and host CD73 synergistically contribute to angiogenesis under tumor condition in vivo . In contrast to above results, another recent study in a model of hind limb ischemia showed that CD73 deficiency had no effect on angiogenesis [46]. Thus, the effect of CD73 on angiogenesis might be different in tumor and nontumor microenvironment.…”

Section: Cd73 and Tumor Angiogenesismentioning

confidence: 68%

The Roles of CD73 in Cancer

Gao

Dong

Zhang

2014

BioMed Research International

165

141

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Purinergic signaling has emerged as an important player in cancer progression and is regulated by a series of nucleotidases. Among the enzyme cascade, CD73, which catelyzes AMP breakdown to adenosine, has been found to be overexpressed in many types of cancer. Various factors and mechanisms are employed to regulate expression of CD73. Accumulating studies have shown that CD73 is a key regulatory molecule of cancer cells proliferation, migration and invasion in vitro, tumor angiogenesis, and tumor immune escape in vivo. With such important roles in cancer, CD73 has become an appealing therapy target. Recent evidences in mice models demonstrated that targeted blockade of CD73 could be a favorable therapeutic approach for cancer patients in the future. In this review, we will summarize the multiple roles of CD73 in cancer development, including its clinical significance, its promotive effects on tumor growth, metastasis, and angiogenesis, and its suppressive effects on immune response, regulatory mechanisms of CD73 expression, and current situation of anti-CD73 cancer therapy.

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Section: Cd73 and Tumor Angiogenesismentioning

confidence: 68%

The Roles of CD73 in Cancer

Gao

Dong

Zhang

2014

BioMed Research International

165

141

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“…It has been shown that ecto-59-nucleotidase/CD73-derived adenosine acts as an endogenous modulator protecting against vascular inflammation and monocyte recruitment, thus limiting the progression of atherosclerosis. Deletion of ecto-59-nucleotidase/CD73 in mice, which leads to a reduction of adenosine, promotes atherogenesis, most likely by de-inhibition of resident macrophages and T cells (Buchheiser et al, 2011), but did not alter angiogenesis (Böring et al, 2013). ET A receptor antagonism restores the myocardial perfusion response to adenosine in experimental hypercholesterolemia (Bonetti et al, 2003).…”

Section: B Atherosclerosis and Coronary Artery Diseasementioning

confidence: 99%

Purinergic Signaling and Blood Vessels in Health and Disease

2013

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“…There are many data in the literature, that indicate adenosine as a proangiogenic factor that stimulates the development of capillaries under the influence of hypoxia. It stimulates endothelial migration, proliferation, and VEGF secretion [19]. Although the adenosine is physiologically present in the extracellular space at very low concentration (<1 mM), it is increased under conditions of metabolic stress.…”

Section: Cd73: Cellular Function and Structurementioning

confidence: 99%

The role of ecto-5′-nucleotidase in endothelial dysfunction and vascular pathologies

Zukowska

Kutryb–Zajac

Toczek

et al. 2015

Pharmacological Reports

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Ecto-5'-nucleotidase (e5NT, CD73) is an enzyme that is highly expressed in endothelium and is involved in the extracellular nucleotide catabolism. CD73 converts AMP to adenosine that via specific subtypes of P1 receptor mediates cytoprotection involving diverse mechanisms such as vasodilatation, suppression of inflammation, inhibition of thrombosis and anti-adrenergic effect. Physiological intravascular concentration of adenosine is in nanomolar range, but could become micromolar in response to various forms of stress. Endothelium is a major site for both CD73 mediated production of adenosine and its cytoprotective effect. Nucleotides (predominantly ATP or ADP) that could be released from different cells via controlled specific of unspecific mechanisms constitute a major source of substrate for adenosine production via CD73. Direct effects of extracellular nucleotides (mediated by P2 receptors) are typically opposite to adenosine P1 mediated activities. Retention of nucleotides and decreased adenosine production due to loss of CD73 function may have negative implications and could be important cause of various pathologies. Protective role of CD73 was indicated in ectopic calcification, atherosclerosis, rejection after xenotransplantation and thrombosis. Reduced activity of CD73 due to lymphocyte contact with endothelium increases its permeability that leads to enhanced leukocyte transmigration. Upregulation of endothelial CD73 may therefore be protective in a number of cardiovascular pathologies. Such effect has been confirmed for some common drugs such as statins and it could be part of its pleiotropic portfolio. Activation of CD73 could be a new target for specific treatment strategy that in particular will enhance endothelial protection.

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Lack of ecto-5′-nucleotidase (CD73) promotes arteriogenesis

Abstract: Serial assessment of dynamic changes of vessel growth and metabolism in the process of arteriogenesis demonstrate that the lack of CD73-derived adenosine importantly promotes arteriogenesis but does not alter angiogenesis in our model of hindlimb ischaemia.

Cited by 21 publications

References 53 publications

The Roles of CD73 in Cancer

The Roles of CD73 in Cancer

Purinergic Signaling and Blood Vessels in Health and Disease

The role of ecto-5′-nucleotidase in endothelial dysfunction and vascular pathologies

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