Targeting endothelial metabolism for anti-angiogenesis therapy: A pharmacological perspective

Missiaen, Rindert; Morales-Rodriguez, Francisco; Eelen, Guy; Carmeliet, Peter

doi:10.1016/j.vph.2017.01.001

Cited by 42 publications

(31 citation statements)

References 170 publications

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“…Likewise, β-oxidation of fatty acids is indispensable for de novo nucleotide production during EC proliferation. In fact, inhibitors of these pathways can target and block proliferation and pathological angiogenesis in vivo [53]. Moreover, TEC can be used for cancer vaccine development.…”

Section: Tumor Endothelial Cells (Tecs)mentioning

confidence: 99%

Tumor microenvironment complexity and therapeutic implications at a glance

et al. 2020

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The dynamic interactions of cancer cells with their microenvironment consisting of stromal cells (cellular part) and extracellular matrix (ECM) components (non-cellular) is essential to stimulate the heterogeneity of cancer cell, clonal evolution and to increase the multidrug resistance ending in cancer cell progression and metastasis. The reciprocal cell-cell/ECM interaction and tumor cell hijacking of non-malignant cells force stromal cells to lose their function and acquire new phenotypes that promote development and invasion of tumor cells. Understanding the underlying cellular and molecular mechanisms governing these interactions can be used as a novel strategy to indirectly disrupt cancer cell interplay and contribute to the development of efficient and safe therapeutic strategies to fight cancer. Furthermore, the tumor-derived circulating materials can also be used as cancer diagnostic tools to precisely predict and monitor the outcome of therapy. This review evaluates such potentials in various advanced cancer models, with a focus on 3D systems as well as lab-on-chip devices.

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Section: Tumor Endothelial Cells (Tecs)mentioning

confidence: 99%

Tumor microenvironment complexity and therapeutic implications at a glance

et al. 2020

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“…It is well‐known that ECs depend mainly on aerobic glycolysis to generate angiogenesis . Thereupon, a novel therapeutic paradigm which regulates ECs metabolism and targets ECs glycolysis for pathological angiogenesis has been highlighted . To date, growing evidence manifests that targeting ECs glycolysis is effective in inhibiting pathological angiogenesis .…”

Section: Discussionmentioning

confidence: 99%

“…In the above studies, most of the described effects of RST on reduction of glycolysis, as evidenced by decreased glucose uptake and lactate production, were corroborated to be mediated by PI3K/Akt and mTOR signalling. Notably, emerging evidence indicates that glycolysis is the major ATP‐producing metabolic pathway in ECs even though the oxygen levels in the bloodstream are amongst the highest in the mammalian body . Thus, a possible association between the glycolytic effects of RST with its anti‐angiogenesis properties deserves to be unravelled.…”

Section: Introductionmentioning

confidence: 99%

Resveratrol inhibits VEGF‐induced angiogenesis in human endothelial cells associated with suppression of aerobic glycolysis via modulation of PKM2 nuclear translocation

Shi³

et al. 2018

Clin Exp Pharma Physio

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Endothelial cells (ECs) mainly depend on aerobic glycolysis to generate angiogenesis. Deregulation of glycolysis is often observed in human endothelial cells during angiogenesis. In the present study, we first report that resveratrol (RST), which has been intensively studied in glucose metabolism of various cancer cells, has a profound inhibitory effect on tube formation and migration via suppression of glycolysis in human umbilical vein endothelial cells (HUVECs) induced by vascular endothelial growth factor (VEGF). Moreover, we further reveal that RST reduced the mRNA and protein level of glucose transporter-1(GLUT1), hexokinase II (HK2), phosphofructokinase-1(PFK1) and pyruvate kinase M2 (PKM2) through modulation of ERK-mediated PKM2 nuclear translocation. Our results provide a novel mechanism to account for the inhibition of RST on VEGF-mediated angiogenesis and suggest that targeting aerobic glycolysis or nuclear PKM2 may be a new approach for pathological angiogenesis prevention or treatment.

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“…One of the long chain fatty acids transporters in ECs is CD36. Inhibition of CD36 has been shown to reduce angiogenesis, but it is not clear whether this effect is due to fatty acid uptake inhibition or not …”

Section: Metabolism Of Cells At the Tumor Microenvironmentmentioning

confidence: 99%

“…Metabolism of ECs is summarized in Figure . For additional information, we encourage our readers to visit some recent reviews on EC metabolism summarizing what is known about glucose, glutamine, and fatty acid fate in these cells …”

Section: Metabolism Of Cells At the Tumor Microenvironmentmentioning

confidence: 99%

Metabolism within the tumor microenvironment and its implication on cancer progression: An ongoing therapeutic target

Ocaña

Martínez‐Poveda

Quesada

et al. 2018

Medicinal Research Reviews

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Since reprogramming energy metabolism is considered a new hallmark of cancer, tumor metabolism is again in the spotlight of cancer research. Many studies have been carried out and many possible therapies have been developed in the last years. However, tumor cells are not alone. A series of extracellular components and stromal cells, such as endothelial cells, cancer-associated fibroblasts, tumor-associated macrophages, and tumor-infiltrating T cells, surround tumor cells in the so-called tumor microenvironment (TME).Metabolic features of these cells are being studied in deep in order to find relationships between metabolism within the TME and tumor progression. Moreover, it cannot be forgotten that tumor growth is able to modulate host metabolism and homeostasis, so that TME is not the whole story. Importantly, the metabolic switch in cancer is just a consequence of the flexibility and adaptability of metabolism and should not be surprising. Treatments of cancer patients with

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Targeting endothelial metabolism for anti-angiogenesis therapy: A pharmacological perspective

Cited by 42 publications

References 170 publications

Tumor microenvironment complexity and therapeutic implications at a glance

Tumor microenvironment complexity and therapeutic implications at a glance

Resveratrol inhibits VEGF‐induced angiogenesis in human endothelial cells associated with suppression of aerobic glycolysis via modulation of PKM2 nuclear translocation

Metabolism within the tumor microenvironment and its implication on cancer progression: An ongoing therapeutic target

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