scholarly journals From Sprouting Angiogenesis to Erythrocytes Generation by Cancer Stem Cells: Evolving Concepts in Tumor Microcirculation

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Raafat S. Alameddine ◽  
Lana Hamieh ◽  
Ali Shamseddine
Keyword(s):  
De Novo ◽  
Antiangiogenic Therapy ◽  
Tumor Resistance ◽  
Sprouting Angiogenesis ◽  
Hypoxic Conditions ◽  
Vessel Growth ◽  
Substantial Progress ◽  
Tumor Growth And Metastasis ◽  
Vascular Mimicry ◽  
Tumor Microcirculation

Angiogenesis is essential for tumor growth and metastasis. Over the last decades, a substantial progress has been achieved in defining different patterns of tumor microcirculation. Sprouting angiogenesis, the oldest model of microcirculation, is the de novo vessel formation from preexisting blood vessels. Vessel splitting and hijacking, also known, respectively, as intussusception and cooption, are alternative models that account for tumor resistance to antiangiogenic therapy. In addition to remodeling the microenvironment, the tumor cell can undergo intrinsic changes and survive hypoxic conditions by acquiring stem cell properties. In line with the concept of pluripotency, tumor cells can form vascular mimicry structures creating their own microcirculation despite a latent vessel growth. The recent identification of the polyploid giant cancer cells and tumor-derived erythrocytes is the most innovative survival mechanism in hypoxia and provides a potential target for more effective therapies.

Abstract 269: 5-aminoimidazole-4-carboxamide-3-ribonucleoside (AICAR) Decreases Soluble Fms-like Tyrosine Kinase-1 (sFlt-1) and Attenuates Endoplasmic Reticulum Stress in Rat Placental Villi Explants

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Christopher T Banek ◽  
Haley E Gillham ◽  
Sarah M Johnson ◽  
Hans C Dreyer ◽  
Jeffrey S Gilbert
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
De Novo ◽  
Vegf Receptor ◽  
Sprague Dawley ◽  
Hypoxic Conditions ◽  
Ampk Phosphorylation ◽  
Angiogenic Balance ◽  
Placental Villi ◽  
Placental Ischemia

Preeclampsia, defined by the onset of de novo hypertension and proteinuria near the 20th week of gestation, is a major contributor to maternal and fetal morbidity and mortality worldwide. Preeclampsia is often preceded by placental ischemia and an imbalance in circulating angiogenic factors (e.g. VEGF - vascular endothelial growth factor, sFlt-1 - soluble VEGF receptor 1). Recent studies also report increased expression of endoplasmic reticulum (ER) stress products in preeclamptic placentas. Our laboratory recently reported 5-aminoimidazole-4-carboxamide-3-ribonuceloside (AICAR) reduces blood pressure and improves angiogenic balance (increased VEGF, decreased sFlt-1) in rats with placental ischemia-induced hypertension, but the mechanism is unclear. We hypothesized AICAR would decrease sFlt-1, increase AMPK phosphorylation, and decrease ER stress in hypoxic placental villous explants. On day 19 of pregnancy, placentas were isolated from four Sprague-Dawley rats and immediately dissected in ice-cold phosphate-buffered saline. Explants were cultured for 12 hours in physiologic normoxic (8% O2) and hypoxic (1.5% O2) conditions. All experiments were performed in triplicate. VEGF secretion was unaffected by AICAR treatment in both normoxic and hypoxic conditions. AICAR decreased sFlt -1 secretion in hypoxic villi (2147±116 vs. *1411±67, P<0.05). Additionally, AMPK activation ratio was increased with AICAR, and was hypoxic-dependent (8%: 2.9±0.3; 8%+A: 3.3±0.1; 1.5%: 3.5±0.1; 1.5%+A: *4.5±0.01;*P<.05). Moreover, markers of ER stress were increased with hypoxia, and decreased with AICAR treatment (BiP 8%: 1.2±0.2; 8%+A: 1.0±0.0; 1.5%: *8.3±0.7; 1.5%+A: 1.9±0.0.3;*P<.05), (CHOP 8%: 0.5±0.0; 8%+A: 0.3±0.1; 1.5%: *1.7±0.1; 1.5%+A: 0.7±0.1;*P<.05). ATF4 was not changed with hypoxia or AICAR treatment. The present data show that AICAR stimulates AMPK phosphorylation and decreases ER stress response proteins in hypoxic placental villi. Further, the present data support the hypothesis that AICAR restores angiogenic balance by decreasing sFlt-1 rather than increasing VEGF secretion from placental villi. These findings suggest AICAR may improve placental function during pregnancies complicated by placental-ischemia.

Growth regulation of the vascular system: evidence for a metabolic hypothesis

1990 ◽  
Vol 259 (3) ◽  
pp. R393-R404 ◽  
Author(s):  
T. H. Adair ◽  
W. J. Gay ◽  
J. P. Montani
Keyword(s):  
Blood Flow ◽  
Blood Vessels ◽  
Growth Regulation ◽  
Vascular System ◽  
Major Influence ◽  
Control Element ◽  
Hypoxic Conditions ◽  
Control Growth ◽  
Vessel Growth ◽  
Tissue Cells

Prolonged imbalances between the perfusion capabilities of the blood vessels and the metabolic requirements of the tissue cells often lead to modification of the vasculature to satisfy the tissue needs. This homeostatic response appears to be bidirectional, since the vascularity of a tissue can increase or decrease in parallel with primary changes in metabolic rate. The factors that mediate the responses are not well understood, but oxygen has been implicated as a major control element, since vessel growth increases during hypoxic conditions and decreases during hyperoxic conditions. The following feedback control hypothesis may apply to many different physiological situations. Decreased oxygenation causes the tissues to become hypoxic, and this initiates a variety of signals that lead to the growth of blood vessels. The increase in vascularity promotes oxygen delivery to the tissue cells by decreasing diffusion distances, increasing capillary surface area, and increasing the maximum rate of blood flow. When the tissues receive adequate amounts of oxygen even during periods of peak activity, the intermediate effectors return to normal levels, and this negative signal, in turn, stops the further development of the vasculature. Although the effector mechanisms of the hypoxic stimulus are still being investigated, adenosine, which is produced in hypoxic tissues, appears to mediate hypoxia-induced increases in vascularity in some instances. Roles for fibroblast growth factor as well as mechanical factors associated with vasodilation and increased blood flow are postulated. Although blood vessel growth is a multifactorial process, a major influence in its regulation appears to be metabolic need. If this view is correct, it may be found that many of the quantitatively significant factors that control growth in a given vasculature are themselves modulated or controlled by metabolic signals reflecting the nutritional status of the tissues which that vasculature supplies.

scholarly journals Effect of hypoxia on purine metabolism of human skeletal muscle cells

Biotecnia ◽  
2021 ◽  
Vol 23 (2) ◽  
Author(s):  
Tania Zenteno-Savín ◽  
Crisalejandra Rivera-Pérez ◽  
Ramón Gaxiola-Robles ◽  
Norma Olguín-Monroy ◽  
Orlando Lugo-Lugo ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
De Novo ◽  
Muscle Cells ◽  
Adenosine Monophosphate ◽  
Adenosine Diphosphate ◽  
Purine Metabolism ◽  
Inosine Monophosphate Dehydrogenase ◽  
Inosine Monophosphate ◽  
Hypoxic Conditions ◽  
Human Skeletal Muscle Cells

Mammals experience some degree of hypoxia during their lifetime. In response to hypoxic challenge, mammalian cells orchestrate specific responses at transcriptional and posttranslational level which lead to changes in the purine metabolites in order to cope with threatening conditions. The aim of this study was to evaluate the response of the enzymes involved in the purine metabolism of human muscle cells to hypoxic conditions. Muscle cells in culture were exposed to hypoxia and the enzymatic activity of inosine monophosphate dehydrogenase (IMPDH), xanthine oxidase (XO), purine nucleoside phosphorylase (PNP) and hypoxanthine guanine phosphoribosyl transferase (HGPRT) as well as their transcript expression were quantified under normoxic and hypoxic conditions. Purine metabolite (hypoxanthine (HX), xanthine (X), uric acid (UA), inosine monophosphate (IMP), inosine, nicotinamide adenine dinucleotide (NAD+), adenosine, adenosine monophosphate (AMP), adenosine diphosphate (ADP), adenosine triphosphate (ATP), guanosine diphosphate (GDP) and guanosine triphosphate (GTP)) concentrations were also quantified. Significant reduction of IMPDH activity and HX and IMP concentrations (p < 0.05) were observed after hypoxia, suggesting a decrease of de novo synthesis of purines. After hypoxia a global reduction of transcripts was observed, suggesting a reduction of the metabolic machinery of purine metabolism to new steady states that balance ATP demand and ATP supply pathways.

The histone acetyltransferase HBO1 (KAT7) promotes efficient tip cell sprouting during angiogenesis

Development ◽  
2021 ◽  
Author(s):  
Zoe L. Grant ◽  
Peter F. Hickey ◽  
Waruni Abeysekera ◽  
Lachlan Whitehead ◽  
Sabrina M. Lewis ◽  
...  
Keyword(s):  
Histone Acetyltransferase ◽  
Dynamic Changes ◽  
Cell Behaviour ◽  
Tip Cell ◽  
Sprouting Angiogenesis ◽  
A Genome ◽  
Vessel Growth ◽  
Intergenic Regions ◽  
Tip Cells

Blood vessel growth and remodelling are essential during embryonic development and disease pathogenesis. The diversity of endothelial cells (ECs) is transcriptionally evident and ECs undergo dynamic changes in gene expression during vessel growth and remodelling. Here, we investigated the role of the histone acetyltransferase HBO1 (KAT7), which is important for activating genes during development and histone H3 lysine 14 acetylation (H3K14ac). Loss of HBO1 and H3K14ac impaired developmental sprouting angiogenesis and reduced pathological EC overgrowth in the retinal endothelium. Single-cell RNA-sequencing of retinal ECs revealed an increased abundance of tip cells in Hbo1 deleted retinas, which lead to EC overcrowding in the retinal sprouting front and prevented efficient tip cell migration. We found that H3K14ac was highly abundant in the endothelial genome in both intra- and intergenic regions suggesting that the role of HBO1 is as a genome organiser that promotes efficient tip cell behaviour necessary for sprouting angiogenesis.

scholarly journals CXCR2-Expressing Tumor Cells Drive Vascular Mimicry in Antiangiogenic Therapy–Resistant Glioblastoma

Neoplasia ◽  
2018 ◽  
Vol 20 (10) ◽  
pp. 1070-1082 ◽  
Author(s):  
Kartik Angara ◽  
Thaiz F. Borin ◽  
Mohammad H. Rashid ◽  
Iryna Lebedyeva ◽  
Roxan Ara ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Antiangiogenic Therapy ◽  
Vascular Mimicry

scholarly journals Recent Advancements of Nanomedicine towards Antiangiogenic Therapy in Cancer

2020 ◽  
Vol 21 (2) ◽  
pp. 455 ◽  
Author(s):  
Anubhab Mukherjee ◽  
Vijay Sagar Madamsetty ◽  
Manash K. Paul ◽  
Sudip Mukherjee
Keyword(s):  
Wound Healing ◽  
Cancer Therapy ◽  
Crucial Role ◽  
Potential Application ◽  
De Novo ◽  
Antiangiogenic Therapy ◽  
Antiangiogenic Agents ◽  
Future Perspectives ◽  
Therapeutic Drugs ◽  
Recent Developments

Angiogenesis is a process of generation of de-novo blood vessels from already existing vasculature. It has a crucial role in different physiological process including wound healing, embryonic development, and tumor growth. The methods by which therapeutic drugs inhibit tumor angiogenesis are termed as anti-angiogenesis cancer therapy. Developments of angiogenic inhibiting drugs have various limitations causing a barrier for successful treatment of cancer, where angiogenesis plays an important role. In this context, investigators developed novel strategies using nanotechnological approaches that have demonstrated inherent antiangiogenic properties or used for the delivery of antiangiogenic agents in a targeted manner. In this present article, we decisively highlight the recent developments of various nanoparticles (NPs) including liposomes, lipid NPs, protein NPs, polymer NPs, inorganic NPs, viral and bio-inspired NPs for potential application in antiangiogenic cancer therapy. Additionally, the clinical perspectives, challenges of nanomedicine, and future perspectives are briefly analyzed.

scholarly journals Antiangiogenic Therapy and Mechanisms of Tumor Resistance in Malignant Glioma

2010 ◽  
Vol 2010 ◽  
pp. 1-16 ◽  
Author(s):  
Ruman Rahman ◽  
Stuart Smith ◽  
Cheryl Rahman ◽  
Richard Grundy
Keyword(s):  
Malignant Glioma ◽  
Antiangiogenic Therapy ◽  
Malignant Gliomas ◽  
Tube Formation ◽  
Endothelial Cell Proliferation ◽  
Vegf Receptor ◽  
Tumor Resistance ◽  
Angiogenic Therapy ◽  
Dismal Prognosis ◽  
Receptor Signal

Despite advances in surgery, radiation therapy, and chemotherapeutics, patients with malignant glioma have a dismal prognosis. The formations of aberrant tumour vasculature and glioma cell invasion are major obstacles for effective treatment. Angiogenesis is a key event in the progression of malignant gliomas, a process involving endothelial cell proliferation, migration, reorganization of extracellular matrix and tube formation. Such processes are regulated by the homeostatic balance between proangiogenic and antiangiogenic factors, most notably vascular endothelial growth factors (VEGFs) produced by glioma cells. Current strategies targeting VEGF-VEGF receptor signal transduction pathways, though effective in normalizing abnormal tumor vasculature, eventually result in tumor resistance whereby a highly infiltrative and invasive phenotype may be adopted. Here we review recent anti-angiogenic therapy for malignant glioma and highlight implantable devices and nano/microparticles as next-generation methods for chemotherapeutic delivery. Intrinsic and adaptive modes of glioma resistance to anti-angiogenic therapy will be discussed with particular focus on the glioma stem cell paradigm.

Possible Role of Local Hypoxia in the De Novo Formation of Dural and Osteodural Arteriovenous Fistulas after Encephalitis

2008 ◽  
Vol 21 (5) ◽  
pp. 698-703 ◽  
Author(s):  
Y. Iizuka ◽  
Y. Yamashiro ◽  
M. Suzuki ◽  
Y. Sumi ◽  
H. Oizumi ◽  
...  
Keyword(s):  
Rare Case ◽  
De Novo ◽  
Initial Step ◽  
Tissue Hypoxia ◽  
Local Tissue ◽  
Arteriovenous Fistulas ◽  
Sprouting Angiogenesis ◽  
Dural Arteriovenous Fistulas

A rare case of de novo formation of dural and osteodural arteriovenous fistulas after encephalitis is presented. We review and discuss the etiological angiogenetic factors and processes in intracranial dural arteriovenous fistulas formation. Local tissue hypoxia may have played a role in the initial step causing sprouting angiogenesis as the main pathogenesis of DAVFs formation.

scholarly journals Contact-Inhibited Chemotaxis in De Novo and Sprouting Blood-Vessel Growth

2008 ◽  
Vol 4 (9) ◽  
pp. e1000163 ◽  
Author(s):  
Roeland M. H. Merks ◽  
Erica D. Perryn ◽  
Abbas Shirinifard ◽  
James A. Glazier
Keyword(s):  
Blood Vessel ◽  
De Novo ◽  
Vessel Growth

scholarly journals The Critical Role of Tetrahydrobiopterin (BH4) Metabolism in Modulating Radiosensitivity: BH4/NOS Axis as an Angel or a Devil

2021 ◽  
Vol 11 ◽  
Author(s):  
Yang Feng ◽  
Yahui Feng ◽  
Liming Gu ◽  
Pengfei Liu ◽  
Jianping Cao ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Free Radicals ◽  
Ionizing Radiation ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Antiangiogenic Therapy ◽  
Critical Role ◽  
Cellular Radiosensitivity ◽  
Normal Tissues

Ionizing radiation and radioactive materials have been widely used in industry, medicine, science and military. The efficacy of radiotherapy and adverse effects of normal tissues are closed related to cellular radiosensitivity. Molecular mechanisms underlying radiosensitivity are of significance to tumor cell radiosensitization as well as normal tissue radioprotection. 5,6,7,8-Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide synthases (NOS) and aromatic amino acid hydroxylases, and its biosynthesis involves de novo biosynthesis and a pterin salvage pathway. In this review we overview the role of BH4 metabolism in modulating radiosensitivity. BH4 homeostasis determines the role of NOS, affecting the production of nitric oxide (NO) and oxygen free radicals. Under conditions of oxidative stress, such as UV-radiation and ionizing radiation, BH4 availability is diminished due to its oxidation, which subsequently leads to NOS uncoupling and generation of highly oxidative free radicals. On the other hand, BH4/NOS axis facilitates vascular normalization, a process by which antiangiogenic therapy corrects structural and functional flaws of tumor blood vessels, which enhances radiotherapy efficacy. Therefore, BH4/NOS axis may serve as an angel or a devil in regulating cellular radiosensitivity. Finally, we will address future perspectives, not only from the standpoint of perceived advances in treatment, but also from the potential mechanisms. These advances have demonstrated that it is possible to modulate cellular radiosensitivity through BH4 metabolism.

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