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Cancers
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Role of Endothelial Cell Metabolism in Normal and Tumor Vasculature
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Role of Endothelial Cell Metabolism in Normal and Tumor Vasculature

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Tumor Microenvironment".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 17687

Special Issue Editor

Prof. Dr. Alessio D'Alessio

E-Mail Website
Guest Editor
Department of Life Science and Public Health, Section of Histology and Embryology, Catholic University of The Sacred Heart, School of Medicine “A. Gemelli”, Largo Francesco Vito, 1 - 00168 Rome, Italy
Interests: signaling pathways; signal transduction; apoptosis; cancer biology; cell culture; PCR; inflammation; stem cell biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Endothelial cells (ECs) that line the inner surface of blood vessels play a critical role in maintaining vascular homeostasis, guaranteeing appropriate oxygen and nutrient supply to all organs, the development of a non-thrombogenic surface, and play a role in the immune surveillance against foreign pathogens. Therefore, the inability of the endothelium to carry out these crucial homeostatic functions, a condition commonly known as endothelial dysfunction, is considered a typical hallmark in the development of vascular pathologies. ECs, which are largely found in a quiescent state in adulthood, can efficiently switch to an active phenotype in response to specific cues that restore their proliferative, migratory, and angiogenic capacity. In cancers, the largely disorganized blood vessel network, as well as the occurring of abnormal angiogenesis, suggest the importance of vascular endothelium as a major therapeutic target to counteract tumor development and progression. Although anti-angiogenic therapy, mainly through the blockade of the VEGF signaling, has received substantial attention in the field of oncology, it results ineffective in many cancers, due to the development of tumor resistance to treatment as well as the activation of compensatory mechanisms. Therefore, there is an urgent need to develop new strategies aimed at inhibiting tumor angiogenesis. The similar metabolic condition of ECs and tumor cells, both relying on high rates of glycolysis rather than oxidative phosphorylation for their energy needs, opens novel routes of investigation of normal and pathological angiogenesis. The main aim of this Special Issue is to call attention to the molecular mechanisms contributing to the metabolic switch in ECs, that may lead to potential endothelium-based therapeutics alternative to anti-angiogenic therapy.

Prof. Alessio D'Alessio
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Angiogenesis
  • Anti-Angiogenic Therapy
  • Cancer Cell Metabolism
  • Endothelial Cell Metabolism
  • Endothelial Dysfunction
  • Glycolysis
  • Hypoxia
  • Vascular Metabolism

Published Papers (7 papers)

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Editorial

Jump to: Research, Review

4 pages, 914 KiB  
Editorial
Role of Endothelial Cell Metabolism in Normal and Tumor Vasculature
by Alessio D’Alessio
Cancers 2023, 15(7), 1921; https://doi.org/10.3390/cancers15071921 - 23 Mar 2023
Viewed by 1949
Abstract
Endothelial cells (ECs) form a simple squamous epithelium, the endothelium, which lines the lumen of all blood vessels and the heart [...] Full article
(This article belongs to the Special Issue Role of Endothelial Cell Metabolism in Normal and Tumor Vasculature)
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Research

Jump to: Editorial, Review

16 pages, 3280 KiB  
Article
Survival Benefit of Statin with Anti-Angiogenesis Efficacy in Lung Cancer-Associated Pleural Fluid through FXR Modulation
by Chen-Liang Tsai, Chih-Ying Changchien, Ying Chen, Chine-Rui Lai, Tzu-Min Chen, Hsin-Han Chang, Wen-Chiuan Tsai, Yu-Ling Tsai, Hao-Chung Tsai, Hung-Yi Lin, Chieh-Yung Wang, Ming-Sheng Shen and Yu-Huei Lin
Cancers 2022, 14(11), 2765; https://doi.org/10.3390/cancers14112765 - 02 Jun 2022
Cited by 4 | Viewed by 2042
Abstract
Lung cancer-related pleural fluid (LCPF) presents as a common complication with limited treatment. Beyond its function in lipid digestion, bile acid was identified as a potent carcinogen to stimulate tumor proliferation. Previous research indicated a correlation between serum bile acid levels and the [...] Read more.
Lung cancer-related pleural fluid (LCPF) presents as a common complication with limited treatment. Beyond its function in lipid digestion, bile acid was identified as a potent carcinogen to stimulate tumor proliferation. Previous research indicated a correlation between serum bile acid levels and the risk of developing several gastrointestinal cancers. Our study identified elevated bile acid levels in LCPF and increased farnesoid X receptor (FXR) expression as bile acid nuclear receptors in pleural microvessels of lung adenocarcinoma. Additionally, LCPF stimulated the expression of proteins involved in bile acid synthesis and cholesterol metabolism in HUVECs including CYP7A1, StAR, HMGCR, and SREBP2. LCPF-induced endothelial motility and angiogenesis were counteracted by using β-muricholic acid as an FXR antagonist. Moreover, we investigated the efficacy of cholesterol-lowering medications, such as cholestyramine, fenofibrate, and atorvastatin, in regulating LCPF-regulated angiogenesis. Along with suppressing endothelial proliferation and angiogenesis, atorvastatin treatment reversed cholesterol accumulation and endothelial junction disruption caused by LCPF. Statin treatment inhibited LCPF-induced endothelial FXR expression as well as the downstream proteins RXR and SHP. Based on the positive findings of suppressing endothelial angiogenesis, our group further incorporated the effect of statin on clinical patients complicated with LCPF. A Kaplan–Meier analysis revealed the clinical benefit of statin exposure in patients with lung adenocarcinoma with LCPF. Conclusively, our study demonstrated the ability of statin to alleviate LCPF-induced angiogenesis in patients with LCPF via FXR modulation. Full article
(This article belongs to the Special Issue Role of Endothelial Cell Metabolism in Normal and Tumor Vasculature)
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Review

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17 pages, 1442 KiB  
Review
Dynamic Interactions between Tumor Cells and Brain Microvascular Endothelial Cells in Glioblastoma
by Erika Testa, Claudia Palazzo, Roberta Mastrantonio and Maria Teresa Viscomi
Cancers 2022, 14(13), 3128; https://doi.org/10.3390/cancers14133128 - 27 Jun 2022
Cited by 8 | Viewed by 2442
Abstract
GBM is the most aggressive brain tumor among adults. It is characterized by extensive vascularization, and its further growth and recurrence depend on the formation of new blood vessels. In GBM, tumor angiogenesis is a multi-step process involving the proliferation, migration and differentiation [...] Read more.
GBM is the most aggressive brain tumor among adults. It is characterized by extensive vascularization, and its further growth and recurrence depend on the formation of new blood vessels. In GBM, tumor angiogenesis is a multi-step process involving the proliferation, migration and differentiation of BMECs under the stimulation of specific signals derived from the cancer cells through a wide variety of communication routes. In this review, we discuss the dynamic interaction between BMECs and tumor cells by providing evidence of how tumor cells hijack the BMECs for the formation of new vessels. Tumor cell–BMECs interplay involves multiple routes of communication, including soluble factors, such as chemokines and cytokines, direct cell–cell contact and extracellular vesicles that participate in and fuel this cooperation. We also describe how this interaction is able to modify the BMECs structure, metabolism and physiology in a way that favors tumor growth and invasiveness. Finally, we briefly reviewed the recent advances and the potential future implications of some high-throughput 3D models to better understanding the complexity of BMECs–tumor cell interaction. Full article
(This article belongs to the Special Issue Role of Endothelial Cell Metabolism in Normal and Tumor Vasculature)
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19 pages, 879 KiB  
Review
Cancer-Induced Metabolic Rewiring of Tumor Endothelial Cells
by Jacopo Lidonnici, Massimo M. Santoro and Roxana E. Oberkersch
Cancers 2022, 14(11), 2735; https://doi.org/10.3390/cancers14112735 - 31 May 2022
Cited by 3 | Viewed by 2581
Abstract
Cancer is a leading cause of death worldwide. If left untreated, tumors tend to grow and spread uncontrolled until the patient dies. To support this growth, cancer cells need large amounts of nutrients and growth factors that are supplied and distributed to the [...] Read more.
Cancer is a leading cause of death worldwide. If left untreated, tumors tend to grow and spread uncontrolled until the patient dies. To support this growth, cancer cells need large amounts of nutrients and growth factors that are supplied and distributed to the tumor tissue by the vascular system. The aberrant tumor vasculature shows deep morphological, molecular, and metabolic differences compared to the blood vessels belonging to the non-malignant tissues (also referred as normal). A better understanding of the metabolic mechanisms driving the differences between normal and tumor vasculature will allow the designing of new drugs with a higher specificity of action and fewer side effects to target tumors and improve a patient’s life expectancy. In this review, we aim to summarize the main features of tumor endothelial cells (TECs) and shed light on the critical metabolic pathways that characterize these cells. A better understanding of such mechanisms will help to design innovative therapeutic strategies in healthy and diseased angiogenesis. Full article
(This article belongs to the Special Issue Role of Endothelial Cell Metabolism in Normal and Tumor Vasculature)
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18 pages, 1374 KiB  
Review
Message in a Bottle: Endothelial Cell Regulation by Extracellular Vesicles
by Claudia Palazzo, Alessio D’Alessio and Luca Tamagnone
Cancers 2022, 14(8), 1969; https://doi.org/10.3390/cancers14081969 - 13 Apr 2022
Cited by 10 | Viewed by 2211
Abstract
Intercellular communication is a key biological mechanism that is fundamental to maintain tissue homeostasis. Extracellular vesicles (EVs) have emerged as critical regulators of cell–cell communication in both physiological and pathological conditions, due to their ability to shuttle a variety of cell constituents, such [...] Read more.
Intercellular communication is a key biological mechanism that is fundamental to maintain tissue homeostasis. Extracellular vesicles (EVs) have emerged as critical regulators of cell–cell communication in both physiological and pathological conditions, due to their ability to shuttle a variety of cell constituents, such as DNA, RNA, lipids, active metabolites, cytosolic, and cell surface proteins. In particular, endothelial cells (ECs) are prominently regulated by EVs released by neighboring cell types. The discovery that cancer cell-derived EVs can control the functions of ECs has prompted the investigation of their roles in tumor angiogenesis and cancer progression. In particular, here, we discuss evidence that supports the roles of exosomes in EC regulation within the tumor microenvironment and in vascular dysfunction leading to atherosclerosis. Moreover, we survey the molecular mechanisms and exosomal cargoes that have been implicated in explanations of these regulatory effects. Full article
(This article belongs to the Special Issue Role of Endothelial Cell Metabolism in Normal and Tumor Vasculature)
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18 pages, 1423 KiB  
Review
Endothelial Cell Metabolism in Vascular Functions
by Antonio Filippini, Luca Tamagnone and Alessio D’Alessio
Cancers 2022, 14(8), 1929; https://doi.org/10.3390/cancers14081929 - 11 Apr 2022
Cited by 11 | Viewed by 2712
Abstract
The endothelium is the innermost layer of all blood and lymphatic vessels composed of a monolayer of specialized endothelial cells (ECs). It is regarded as a dynamic and multifunctional endocrine organ that takes part in essential processes, such as the control of blood [...] Read more.
The endothelium is the innermost layer of all blood and lymphatic vessels composed of a monolayer of specialized endothelial cells (ECs). It is regarded as a dynamic and multifunctional endocrine organ that takes part in essential processes, such as the control of blood fluidity, the modulation of vascular tone, the regulation of immune response and leukocyte trafficking into perivascular tissues, and angiogenesis. The inability of ECs to perform their normal biological functions, known as endothelial dysfunction, is multi-factorial; for instance, it implicates the failure of ECs to support the normal antithrombotic and anti-inflammatory status, resulting in the onset of unfavorable cardiovascular conditions such as atherosclerosis, coronary artery disease, hypertension, heart problems, and other vascular pathologies. Notably, it is emerging that the ability of ECs to adapt their metabolic status to persistent changes of the tissue microenvironment could be vital for the maintenance of vascular functions and to prevent adverse vascular events. The main purpose of the present article is to shed light on the unique metabolic plasticity of ECs as a prospective therapeutic target; this may lead to the development of novel strategies for cardiovascular diseases and cancer. Full article
(This article belongs to the Special Issue Role of Endothelial Cell Metabolism in Normal and Tumor Vasculature)
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13 pages, 1465 KiB  
Review
The Emerging Role of Amino Acids of the Brain Microenvironment in the Process of Metastasis Formation
by Francesca Cutruzzolà, Amani Bouzidi, Francesca Romana Liberati, Sharon Spizzichino, Giovanna Boumis, Alberto Macone, Serena Rinaldo, Giorgio Giardina and Alessio Paone
Cancers 2021, 13(12), 2891; https://doi.org/10.3390/cancers13122891 - 09 Jun 2021
Cited by 4 | Viewed by 2778
Abstract
Brain metastases are the most severe clinical manifestation of aggressive tumors. Melanoma, breast, and lung cancers are the types that prefer the brain as a site of metastasis formation, even if the reasons for this phenomenon still remain to be clarified. One of [...] Read more.
Brain metastases are the most severe clinical manifestation of aggressive tumors. Melanoma, breast, and lung cancers are the types that prefer the brain as a site of metastasis formation, even if the reasons for this phenomenon still remain to be clarified. One of the main characteristics that makes a cancer cell able to form metastases in the brain is the ability to interact with the endothelial cells of the microvasculature, cross the blood–brain barrier, and metabolically adapt to the nutrients available in the new microenvironment. In this review, we analyzed what makes the brain a suitable site for the development of metastases and how this microenvironment, through the continuous release of neurotransmitters and amino acids in the extracellular milieu, is able to support the metabolic needs of metastasizing cells. We also suggested a possible role for amino acids released by the brain through the endothelial cells of the blood–brain barrier into the bloodstream in triggering the process of extravasation/invasion of the brain parenchyma. Full article
(This article belongs to the Special Issue Role of Endothelial Cell Metabolism in Normal and Tumor Vasculature)
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