scholarly journals 3D tumor angiogenesis models: recent advances and challenges

2021 ◽  
Author(s):  
Sharath M. Bhat ◽  
Vaishnavi A. Badiger ◽  
Sampara Vasishta ◽  
Juhi Chakraborty ◽  
Seetharam Prasad ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tumor Angiogenesis ◽  
Vasculogenic Mimicry ◽  
Model Systems ◽  
Quantitative Expression ◽  
Vascular Model ◽  
Sequencing Technologies ◽  
Organ Systems ◽  
Endothelial Cell Heterogeneity ◽  
Underlying Mechanisms

AbstractThe development of blood vessels, referred to as angiogenesis, is an intricate process regulated spatially and temporally through a delicate balance between the qualitative and quantitative expression of pro and anti-angiogenic molecules. As angiogenesis is a prerequisite for solid tumors to grow and metastasize, a variety of tumor angiogenesis models have been formulated to better understand the underlying mechanisms and associated clinical applications. Studies have demonstrated independent mechanisms inducing angiogenesis in tumors such as (a) HIF-1/VEGF mediated paracrine interactions between a cancer cell and endothelial cells, (b) recruitment of progenitor endothelial cells, and (c) vasculogenic mimicry. Moreover, single-cell sequencing technologies have indicated endothelial cell heterogeneity among organ systems including tumor tissues. However, existing angiogenesis models often rely upon normal endothelial cells which significantly differ from tumor endothelial cells exhibiting distinct (epi)genetic and metabolic signatures. Besides, the existence of intra-individual variations necessitates the development of improved tumor vascular model systems for personalized medicine. In the present review, we summarize recent advancements of 3D tumor vascular model systems which include (a) tissue engineering-based tumor models; (b) vascular organoid models, and (c) organ-on-chips and their importance in replicating the tumor angiogenesis along with the associated challenges to design improved models.

scholarly journals Tumor Blood Vessels and Vasculogenic Mimicry – Current Knowledge and Searching for New Cellular/Molecular Targets of Anti-Angiogenic Therapy

2017 ◽  
Vol 5 (1) ◽  
pp. 50-71 ◽  
Author(s):  
Agnieszka Knopik-Skrocka ◽  
Patrycja Kręplewska ◽  
Donata Jarmołowska-Jurczyszyn
Keyword(s):  
Endothelial Cells ◽  
Blood Vessels ◽  
Tumor Angiogenesis ◽  
Current Knowledge ◽  
Vasculogenic Mimicry ◽  
High Plasticity ◽  
Drug Induced ◽  
Cellular Targets ◽  
Angiogenic Therapy ◽  
And Migration

SummaryBlood vessel formation in tumor is defined as tumor angiogenesis. So far, the most known its mechanism is sprouting, which means formation of blood vessels from existing ones, as a result of the proliferation and migration of endothelial cells. The main mitogenic factor of these cells is vascular endothelial growth factor VEGF, acting by VEGFR-2 receptors. Recent studies have provided knowledge about the ability of tumors to form vessel-like structures. The phenomenon was called vascular mimicry. Tumor cells show a high plasticity and they can undergo differentiation to the ones with phenotype similar to endothelial cells. Each of the known tumor angiogenesis mechanisms is a result of many different factors and cell cooperation in tumor microenvironment. Tumor ability to the heterogeneous vascularization forces developing of complex, anti-angiogenic therapy directed to different molecular and cellular targets. Therapies, used so far, often lead to drug-induced hypoxia, which increases tumor cell aggressiveness and metastasis.

scholarly journals Homocysteine Induces Apoptosis of Human Umbilical Vein Endothelial Cells via Mitochondrial Dysfunction and Endoplasmic Reticulum Stress

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Zhimin Zhang ◽  
Congying Wei ◽  
Yanfen Zhou ◽  
Tao Yan ◽  
Zhengqiang Wang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Er Stress ◽  
Mitochondrial Dysfunction ◽  
Umbilical Vein ◽  
Dependent Manner ◽  
Human Umbilical Vein ◽  
Homologous Protein ◽  
Intracellular Ros ◽  
Underlying Mechanisms ◽  
Umbilical Vein Endothelial Cells

Homocysteine- (Hcy-) induced endothelial cell apoptosis has been suggested as a cause of Hcy-dependent vascular injury, while the proposed molecular pathways underlying this process are unclear. In this study, we investigated the adverse effects of Hcy on human umbilical vein endothelial cells (HUVEC) and the underlying mechanisms. Our results demonstrated that moderate-dose Hcy treatment induced HUVEC apoptosis in a time-dependent manner. Furthermore, prolonged Hcy treatment increased the expression of NOX4 and the production of intracellular ROS but decreased the ratio of Bcl-2/Bax and mitochondrial membrane potential (MMP), resulting in the leakage of cytochrome c and activation of caspase-3. Prolonged Hcy treatment also upregulated glucose-regulated protein 78 (GRP78), activated protein kinase RNA-like ER kinase (PERK), and induced the expression of C/EBP homologous protein (CHOP) and the phosphorylation of NF-κb. The inhibition of NOX4 decreased the production of ROS and alleviated the Hcy-induced HUVEC apoptosis and ER stress. Blocking the PERK pathway partly alleviated Hcy-induced HUVEC apoptosis and the activation of NF-κb. Taken together, our results suggest that Hcy-induced mitochondrial dysfunction crucially modulated apoptosis and contributed to the activation of ER stress in HUVEC. The excessive activation of the PERK pathway partly contributed to Hcy-induced HUVEC apoptosis and the phosphorylation of NF-κb.

scholarly journals The Cellular Choreography of Osteoblast Angiotropism in Bone Development and Homeostasis

2021 ◽  
Vol 22 (14) ◽  
pp. 7253
Author(s):  
Georgiana Neag ◽  
Melissa Finlay ◽  
Amy J. Naylor
Keyword(s):  
Endothelial Cells ◽  
Bone Formation ◽  
Drug Targets ◽  
Bone Development ◽  
Cell Types ◽  
Regulatory Relationship ◽  
Sequencing Technologies ◽  
Resolution Imaging ◽  
Molecular Relationships ◽  
Form Type

Interaction between endothelial cells and osteoblasts is essential for bone development and homeostasis. This process is mediated in large part by osteoblast angiotropism, the migration of osteoblasts alongside blood vessels, which is crucial for the homing of osteoblasts to sites of bone formation during embryogenesis and in mature bones during remodeling and repair. Specialized bone endothelial cells that form “type H” capillaries have emerged as key interaction partners of osteoblasts, regulating osteoblast differentiation and maturation and ensuring their migration towards newly forming trabecular bone areas. Recent revolutions in high-resolution imaging methodologies for bone as well as single cell and RNA sequencing technologies have enabled the identification of some of the signaling pathways and molecular interactions that underpin this regulatory relationship. Similarly, the intercellular cross talk between endothelial cells and entombed osteocytes that is essential for bone formation, repair, and maintenance are beginning to be uncovered. This is a relatively new area of research that has, until recently, been hampered by a lack of appropriate analysis tools. Now that these tools are available, greater understanding of the molecular relationships between these key cell types is expected to facilitate identification of new drug targets for diseases of bone formation and remodeling.

scholarly journals Inhibition of AngiogenesisIn Vitroby Chebulagic Acid: A COX-LOX Dual Inhibitor

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
A. P. Athira ◽  
A. Helen ◽  
K. Saja ◽  
P. Reddanna ◽  
P. R. Sudhakaran
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Model Systems ◽  
Antiangiogenic Effect ◽  
Dual Inhibitor ◽  
Endogenous Factors ◽  
Human Umbilical Vein ◽  
Chebulagic Acid ◽  
Vessel Growth ◽  
Umbilical Vein Endothelial Cells

Angiogenesis is a crucial step in the growth of cancer and its metastasis. It is regulated by several endogenous factors which may stimulate or inhibit the new blood vessel growth. Besides these endogenous factors, several exogenous factors including some natural compounds are known to modulate angiogenesis. Angiogenesis being a potential target for drugs against a number of pathological conditions, search for compounds from natural sources that can affect angiogenesis is of great interest. The objective of our present study was to understand the effect of chebulagic acid, a COX-LOX dual inhibitor isolated from the fruits ofTerminalia chebulaRetz., on angiogenesis. The model systems used were rat aortic rings and human umbilical vein endothelial cells. The results showed that chebulagic acid exerts an antiangiogenic effect. This was evidenced from decreased sprouting in rat aortic rings and decrease in biochemical markers in endothelial cells treated with chebulagic acid. It downregulated the production of CD31, E-selectin, and vascular endothelial growth factor in human umbilical vein endothelial cells in culture (HUVEC). Further studies to understand the molecular mechanism of action of chebulagic acid revealed that CA exerts its anti angiogenic effect by modulating VE cadherin-βcatenin signalling in human umbilical vein endothelial cells.

scholarly journals Development of preclinical and clinical models for immune-related adverse events following checkpoint immunotherapy: a perspective from SITC and AACR

2021 ◽  
Vol 9 (9) ◽  
pp. e002627
Author(s):  
Nicholas L Bayless ◽  
Jeffrey A Bluestone ◽  
Samantha Bucktrout ◽  
Lisa H Butterfield ◽  
Elizabeth M Jaffee ◽  
...  
Keyword(s):  
Adverse Events ◽  
Cancer Immunotherapy ◽  
Immune Cell ◽  
Cytotoxic T Lymphocyte ◽  
Action Plan ◽  
Treatment Strategies ◽  
Model Systems ◽  
Preclinical Model ◽  
Programmed Death ◽  
Organ Systems

Recent advances in cancer immunotherapy have completely revolutionized cancer treatment strategies. Nonetheless, the increasing incidence of immune-related adverse events (irAEs) is now limiting the overall benefits of these treatments. irAEs are well-recognized side effects of some of the most effective cancer immunotherapy agents, including antibody blockade of the cytotoxic T-lymphocyte-associated protein 4 and programmed death protein 1/programmed-death ligand 1 pathways. To develop an action plan on the key elements needed to unravel and understand the key mechanisms driving irAEs, the Society for Immunotherapy for Cancer and the American Association for Cancer Research partnered to bring together research and clinical experts in cancer immunotherapy, autoimmunity, immune regulation, genetics and informatics who are investigating irAEs using animal models, clinical data and patient specimens to discuss current strategies and identify the critical next steps needed to create breakthroughs in our understanding of these toxicities. The genetic and environmental risk factors, immune cell subsets and other key immunological mediators and the unique clinical presentations of irAEs across the different organ systems were the foundation for identifying key opportunities and future directions described in this report. These include the pressing need for significantly improved preclinical model systems, broader collection of biospecimens with standardized collection and clinical annotation made available for research and integration of electronic health record and multiomic data with harmonized and standardized methods, definitions and terminologies to further our understanding of irAE pathogenesis. Based on these needs, this report makes a set of recommendations to advance our understanding of irAE mechanisms, which will be crucial to prevent their occurrence and improve their treatment.

scholarly journals VE-PTP participates in vasculogenic mimicry by preventing autophagic degradation of VE-cadherin

2019 ◽  
Author(s):  
Daniel Delgado-Bellido ◽  
Concepción Bueno-Galera ◽  
Angel Garcia-Diaz ◽  
F. Javier Oliver
Keyword(s):  
Endothelial Cells ◽  
Malignant Melanoma ◽  
Tumor Cells ◽  
Malignant Tumor ◽  
Vasculogenic Mimicry ◽  
P120 Catenin ◽  
Human Malignant Melanoma ◽  
Aberrant Phenotype ◽  
Autophagic Degradation ◽  
Vascular Expression

AbstractAberrant extra-vascular expression of VE-cadherin has been observed in metastasis associated with Vasculogenic Mimicry (VM); we have recently shown that in VM prone (VM+) tumor cells VE-cadherin is mainly in the form of pVE-cadherin in Y658 allowing an increased plasticity that potentiates VM development. As excessive VE-cadherin phosphorylation is regulated by the phosphatase VEPTP in endothelial cells in the current study we analysed its role in this aberrant phenotype in malignant tumor cells. We show that human malignant melanoma cells VM+, also express VE-PTP although at lower levels than endothelial cells. The complex VE-PTP/VE-Cadherin/p120-catenin act as a safeguard to prevent VE-cadherin degradation by autophagy. Indeed, silencing of VE-PTP results in complete degradation of VE-cadherin with the features of autophagy and increases the global p120 tyrosine phosphorylation status. In summary, we show that VE-PTP is involved in VM formation and disruption of VE-PTP/VE-Cadherin/p120 complex results in enhanced autophagy in aggressive VM+ cells.

scholarly journals Topological and Metagenomic Evidence For Intensified Bacterial-Fungal Interactions in Mangrove Root Interior

2021 ◽  
Author(s):  
Zhengyuan Zhou ◽  
Ruiwen Hu ◽  
Yanmei Ni ◽  
Wei Zhuang ◽  
Zhiwen Luo ◽  
...  
Keyword(s):  
Plant Performance ◽  
Sequencing Technologies ◽  
Mangrove Root ◽  
Domain Interactions ◽  
Network Topologies ◽  
Mangrove Roots ◽  
Metagenome Sequencing ◽  
Underlying Mechanisms ◽  
Bacteria And Fungi ◽  
Fungal Interactions

Abstract Background: Plant roots host a repertoire of bacteria and fungi, whose ecological interactions could improve their functions and plant performance. However, potential interactions and underlying mechanisms remain largely unknown in root-associated microbial communities at a continuous fine-scale. Results: We analyzed microbial intra- and inter-domain network topologies, keystone taxa, and interaction-related genes across four compartments (non-rhizosphere, rhizosphere, episphere and endosphere) from a soil-mangrove root continuum, using amplicon and metagenome sequencing technologies. We found that both intra- and inter-domain networks displayed notable differences in the structure and topology across four compartments. Compared to three peripheral compartments, the endosphere was a distinctive compartment with more intensive interactions in bacterial-fungal network than in bacterial or fungal network, which could be related to three bacterial keystone taxa (Vibrio, Anaerolineae and Desulfarculaceae) detected in the endosphere as they are known to intensify inter-domain interactions with fungi and stimulate biofilm formation. Also, high abundances of genes involved in cell-cell communications by quorum sensing (rhlI, lasI, pqsH and lasR) and aerobic cobamide biosynthesis (cobG, cobF and cobA) were detected in the endosphere.Conclusions: Our results reveal intensified inter-domain interactions of endophytes in the mangrove roots, creating a distinct micro-environment to promote a biofilm life-style.

Age-Dependent Transcriptional Alterations in Cardiac Endothelial Cells

2021 ◽  
Author(s):  
Uchenna Emechebe ◽  
Jonathan William Nelson ◽  
Nabil J. Alkayed ◽  
Sanjiv Kaul ◽  
Andrew C Adey ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Single Cell ◽  
Significant Risk ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Mouse Heart ◽  
Age Related ◽  
Organ Systems ◽  
Transcriptional Alterations

Aging is a significant risk factor for cardiovascular disease. Despite the fact that endothelial cells play critical roles in cardiovascular function and disease, the molecular impact of aging on this cell population in many organ systems remains unknown. In this study, we sought to determine age-associated transcriptional alterations in cardiac endothelial cells. Highly enriched populations of endothelial cells (ECs) isolated from the heart, brain and kidney of young (3 months) and aged (24 months) C57/BL6 mice were profiled for RNA expression via bulk RNA sequencing. Approximately 700 cardiac endothelial transcripts significantly differ by age. Gene set enrichment analysis indicated similar patterns for cellular pathway perturbations. Receptor-ligand comparisons indicated parallel alterations in age-affected circulating factors and cardiac endothelial-expressed receptors. Single-cell RNA-seq analysis identified 9 distinct endothelial cell subtypes in the heart with an age-associated population shift observed for the Aplnr-enriched endothelial cell clusters. Gene and pathway enrichment analyses show that age-related transcriptional response of cardiac endothelial cells is distinct from that of endothelial cells derived from the brain or kidney vascular bed. Furthermore, single-cell analysis identified 9 distinct EC subtypes, and shows that the Aplnr-enriched subtype is reduced with age in mouse heart. Finally, we identify age-dysregulated genes in specific aged cardiac endothelial subtypes.

Sign in / Sign up

Export Citation Format

Share Document