Tumor angiogenesis: causes, consequences, challenges and opportunities

Cellular and Molecular Life Sciences, Journal Year: 2019, Volume and Issue: 77(9), P. 1745 - 1770

Published: Nov. 6, 2019

Abstract Tumor vascularization occurs through several distinct biological processes, which not only vary between tumor type and anatomic location, but also occur simultaneously within the same cancer tissue. These processes are orchestrated by a range of secreted factors signaling pathways can involve participation non-endothelial cells, such as progenitors or stem cells. Anti-angiogenic therapies using either antibodies tyrosine kinase inhibitors have been approved to treat types cancer. However, benefit treatment has so far modest, some patients responding at all others acquiring resistance. It is becoming increasingly clear that blocking tumors from accessing circulation an easy task accomplish. vessel functionality gene expression often differ vastly when comparing different subtypes, phenotype be markedly heterogeneous single tumor. Here, we summarize current understanding cellular molecular mechanisms involved in angiogenesis discuss challenges opportunities associated with vascular targeting.

Language: Английский

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Angiogenesis Analyzer for ImageJ — A comparative morphometric analysis of “Endothelial Tube Formation Assay” and “Fibrin Bead Assay”

Scientific Reports, Journal Year: 2020, Volume and Issue: 10(1)

Published: July 14, 2020

Abstract Angiogenesis assays based on in vitro capillary-like growth of endothelial cells (EC) are widely used, either to evaluate the effect anti- and pro-angiogenesis drugs interest, or test compare functional capacities various types EC progenitor cells. Among different methods applied study angiogenesis, most commonly used is “Endothelial Tube Formation Assay” (ETFA). In suitable culture conditions, form two-dimensional (2D) branched structures that can lead a meshed pseudo-capillary network. An alternative approach ETFA “Fibrin Bead (FBA), use Cytodex 3 microspheres, which promote 3D patterns from coated EC, for high throughput angiogenesis studies. The analytical evaluation these two still remains challenging terms observation method image analysis. We previously developed “Angiogenesis Analyzer” ImageJ (AA), tool allowing analysis ETFA-derived images, according characteristics networks. this work, we implemented new algorithm AA able recognize microspheres analyze attached FBA model. Such presented first time fully automated mode using non-destructive acquisition. detailed algorithms version both ( i.e . FBA) their efficiency, accuracy statistical relevance model Human Umbilical Vein (HUVEC). Although do not assess same biological step, our data suggest they display specific complementary information processes

Language: Английский

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Targeting Adenosine in Cancer Immunotherapy to Enhance T-Cell Function

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: June 6, 2019

T cells play a critical role in cancer control, but range of potent immunosuppressive mechanisms can be upregulated the tumor microenvironment (TME) to abrogate their activity. While various immunotherapies (IMTs) aiming at re-invigorating T-cell-mediated anti-tumor response, such as immune checkpoint blockade (ICB), and adoptive cell transfer (ACT) natural or gene-engineered ex vivo expanded tumor-specific cells, have led unprecedented clinical responses, only small proportion patients benefit from these treatments. Important research efforts are thus underway identify biomarkers well develop personalized combinatorial approaches that target other inhibitory TME. In recent years, adenosinergic signaling has emerged powerful immuno-metabolic tumors. Like several barriers TME, PD-1/PDL-1 axis, CTLA-4, indoleamine 2,3-dioxygenase (IDO-1), adenosine plays important physiologic roles, been co-opted by tumors promote growth impair immunity. Several agents counteracting axis developed, pre-clinical studies demonstrated activity, alone combination with IMTs including ICB ACT. Here we review regulation levels which it promotes broadly suppresses protective immunity, extra focus on attenuation function. Finally, present an overview promising being explored for blocking enhanced control solid

Language: Английский

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Anti-Angiogenic Therapy: Current Challenges and Future Perspectives

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(7), P. 3765 - 3765

Published: April 5, 2021

Anti-angiogenic therapy is an old method to fight cancer that aims abolish the nutrient and oxygen supply tumor cells through decrease of vascular network avoidance new blood vessels formation. Most anti-angiogenic agents approved for treatment rely on targeting endothelial growth factor (VEGF) actions, as VEGF signaling considered main angiogenesis promotor. In addition control angiogenesis, these drugs can potentiate immune also exhibits immunosuppressive functions. Despite mechanistic rational strongly supports benefit stop progression, they revealed be insufficient in most cases. We hypothesize rehabilitation interfere with mechanisms related microenvironment might represent a promising strategy. this review, we deepened research molecular underlying strategies their failure went further into alternative impact angiogenesis. concluded combinatory effectors angiogenic pathways putative solution therapies.

Language: Английский

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HIFs, angiogenesis, and metabolism: elusive enemies in breast cancer

Journal of Clinical Investigation, Journal Year: 2020, Volume and Issue: 130(10), P. 5074 - 5087

Published: Sept. 1, 2020

Hypoxia-inducible factors (HIFs) and the HIF-dependent cancer hallmarks angiogenesis metabolic rewiring are well-established drivers of breast aggressiveness, therapy resistance, poor prognosis. Targeting HIF its downstream targets in metabolism has been unsuccessful so far clinical setting, with major unresolved challenges residing target selection, development robust biomarkers for response prediction, understanding harnessing escape mechanisms. This Review discusses pathophysiological role HIFs, angiogenesis, targeting these features patients cancer. Rational therapeutic combinations, especially immunotherapy endocrine therapy, seem most promising exploitation intricate interplay cells tumor microenvironment.

Language: Английский

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Unraveling the Role of Angiogenesis in Cancer Ecosystems

Frontiers in Oncology, Journal Year: 2018, Volume and Issue: 8

Published: July 2, 2018

Activation of the tumor and stromal cell-driven angiogenic program is one first requirements in ecosystem for growth dissemination. The understanding dynamic has rapidly evolved over last decades. Beginning with canonical sprouting angiogenesis, followed by vasculogenesis intussusception, finishing vasculogenic mimicry, need different neovascularization mechanisms further explored. In addition, an overview orchestration angiogenesis within cellular molecular components provided. Clinical evidence demonstrated effectiveness traditional vessel-directed anti-angiogenics, stressing on important role establishment, dissemination growth. Particular focus placed interaction between cells their surrounding ecosystem, which now regarded as a promising target development new anti-angiogenics.

Language: Английский

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Pathological angiogenesis: mechanisms and therapeutic strategies

Angiogenesis, Journal Year: 2023, Volume and Issue: 26(3), P. 313 - 347

Published: April 15, 2023

In multicellular organisms, angiogenesis, the formation of new blood vessels from pre-existing ones, is an essential process for growth and development. Different mechanisms such as vasculogenesis, sprouting, intussusceptive, coalescent well vessel co-option, vasculogenic mimicry lymphangiogenesis, underlie vasculature. many pathological conditions, cancer, atherosclerosis, arthritis, psoriasis, endometriosis, obesity SARS-CoV-2(COVID-19), developmental angiogenic processes are recapitulated, but often done so without normal feedback that regulate ordinary spatial temporal patterns formation. Thus, angiogenesis presents challenges yet opportunities design vascular-directed therapies. Here, we provide overview recent insights into development highlight novel therapeutic strategies promote or inhibit to stabilize, reverse, even halt disease progression. our review, will also explore several additional aspects (the switch, hypoxia, angiocrine signals, endothelial plasticity, normalization, cell anergy) operate in parallel canonical speculate how these may be targeted with anti-angiogenic

Language: Английский

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SIRT2: Controversy and multiple roles in disease and physiology

Ageing Research Reviews, Journal Year: 2019, Volume and Issue: 55, P. 100961 - 100961

Published: Sept. 7, 2019

Language: Английский

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M2 Macrophage-Derived Exosomes Promote Angiogenesis and Growth of Pancreatic Ductal Adenocarcinoma by Targeting E2F2

Molecular Therapy, Journal Year: 2020, Volume and Issue: 29(3), P. 1226 - 1238

Published: Nov. 20, 2020

Pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive tumors all over world, has a generally poor prognosis, and its progression is positively correlated with density blood vessels. Recently, tumor-associated macrophages (TAMs) were proven to be beneficial for angiogenesis, but their mechanism action remains unclear. Our study indicated that M2 microvessel (MVD) PDAC tissues, macrophage-derived exosomes (MDEs) could promote angiogenesis mouse aortic endothelial cells (MAECs) in vitro. At same time, MDEs also growth subcutaneous increase vascular mice. Moreover, we found miR-155-5p miR-221-5p levels higher than those M0 MDEs, they transferred into MAECs, as demonstrated by RNA sequencing (RNA-seq) qPCR analysis. data confirmed interaction between TAMs exosomes. Additionally, targeting exosomal miRNAs derived from might provide diagnostic therapeutic strategies PDAC.

Language: Английский

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Use of Human Umbilical Vein Endothelial Cells (HUVEC) as a Model to Study Cardiovascular Disease: A Review

Applied Sciences, Journal Year: 2020, Volume and Issue: 10(3), P. 938 - 938

Published: Jan. 31, 2020

Cardiovascular disease (CVD) is the leading cause of death worldwide, and extensive research has been performed to understand this better, using various experimental models. The endothelium plays a crucial role in development CVD, since it an interface between bloodstream components, such as monocytes platelets, other arterial wall components. Human umbilical vein endothelial cell (HUVEC) isolation from cord was first described 1973. To date, model still widely used because high HUVEC success rate, are excellent study broad array diseases, including cardiovascular metabolic diseases. We here review history isolation, over time, culture characteristics conditions, advantages disadvantages finally, its applications area

Language: Английский

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