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Frontiers in Cell and Developmental... 2021Non-coding RNAs (ncRNAs) are RNAs that do not encode proteins, but perform biological functions in various physiological and pathological processes, including cancer... (Review)
Review
Non-coding RNAs (ncRNAs) are RNAs that do not encode proteins, but perform biological functions in various physiological and pathological processes, including cancer formation, inflammation, and neurological diseases. Tumor blood vessels are a key target for cancer management. A number of factors regulate the angiogenesis of malignant tumors. NcRNAs participate in the regulation of tumor angiogenesis. Abnormal expression of ncRNAs act as tumor suppressors or oncogenes to affect the development of tumors. In this review we summarized the biological functions of ncRNAs, and discussed its regulatory mechanisms in tumor angiogenesis. This article will provide new insights for the research of ncRNAs in tumor angiogenesis.
PubMed: 34616746
DOI: 10.3389/fcell.2021.751578 -
Frontiers in Oncology 2024Angiogenesis is essential for tumour growth and metastasis. Antiangiogenic factor-targeting drugs have been approved as first line agents in a variety of oncology... (Review)
Review
Angiogenesis is essential for tumour growth and metastasis. Antiangiogenic factor-targeting drugs have been approved as first line agents in a variety of oncology treatments. Clinical drugs frequently target the VEGF signalling pathway during sprouting angiogenesis. Accumulating evidence suggests that tumours can evade antiangiogenic therapy through other angiogenesis mechanisms in addition to the vascular sprouting mechanism involving endothelial cells. These mechanisms include (1) sprouting angiogenesis, (2) vasculogenic mimicry, (3) vessel intussusception, (4) vascular co-option, (5) cancer stem cell-derived angiogenesis, and (6) bone marrow-derived angiogenesis. Other non-sprouting angiogenic mechanisms are not entirely dependent on the VEGF signalling pathway. In clinical practice, the conversion of vascular mechanisms is closely related to the enhancement of tumour drug resistance, which often leads to clinical treatment failure. This article summarizes recent studies on six processes of tumour angiogenesis and provides suggestions for developing more effective techniques to improve the efficacy of antiangiogenic treatment.
PubMed: 38590656
DOI: 10.3389/fonc.2024.1359069 -
Cancers Jan 2022Angiogenesis, the formation of new blood vessels from already existing vasculature, is tightly regulated by pro- and anti-angiogenic stimuli and occurs under both... (Review)
Review
Angiogenesis, the formation of new blood vessels from already existing vasculature, is tightly regulated by pro- and anti-angiogenic stimuli and occurs under both physiological and pathological conditions. Tumor angiogenesis is central for tumor development, and an "angiogenic switch" could be initiated by multiple immune cells, such as neutrophils. Tumor-associated neutrophils promote tumor angiogenesis by the release of both conventional and non-conventional pro-angiogenic factors. Therefore, neutrophil-mediated tumor angiogenesis should be taken into consideration in the design of novel anti-cancer therapy. This review recapitulates the complex role of neutrophils in tumor angiogenesis and summarizes neutrophil-derived pro-angiogenic factors and mechanisms regulating angiogenic activity of tumor-associated neutrophils. Moreover, it provides up-to-date information about neutrophil-targeting therapy, complementary to anti-angiogenic treatment.
PubMed: 35158807
DOI: 10.3390/cancers14030536 -
Frontiers in Oncology 2019Generally, changes in the metabolic status of cells under conditions like hypoxia and accumulation of lactate can be sensed by various sensing mechanisms, leading to... (Review)
Review
Generally, changes in the metabolic status of cells under conditions like hypoxia and accumulation of lactate can be sensed by various sensing mechanisms, leading to modulation of a number of signal transduction pathways and transcription factors. Several of the proangiogenic cytokines like VEGF, FGF, PDGF, TGF-β, Ang-2, ILs, etc. are secreted by cancer cells, under hypoxic microenvironment. These cytokines bind to their receptors on the endothelial cells and activates a number of signaling pathways including Akt/PIP3, Src, p38/MAPK, Smad2/3, etc., which ultimately results in the proliferation and migration of endothelial cells. Transcription factors that are activated in response to the metabolic status of tumors include HIFs, NF-κb, p53, El-2, and FOXO. Many of these transcription factors has been reported to be regulated by a class of histone deacetylase called sirtuins. Sirtuins are NAD dependent histone deacetylases that play pivotal role in the regulation of tumor cell metabolism, proliferation, migration and angiogenesis. The major function of sirtuins include, deacetylation of histones as well as some non-histone proteins like NF-κB, FOXOs, PPAR⋎, PGC1-α, enzymes like acetyl coenzymeA and structural proteins like α tubulin. In the cell, sirtuins are generally considered as the redox sensors and their activities are dependent on the metabolic status of the cell. Understanding the intricate regulatory mechanisms adopted by sirtuins, is crucial in devising effective therapeutic strategies against angiogenesis, metastasis and tumor progression. Keeping this in mind, the present review focuses on the role of sirtuins in the process of tumor angiogenesis and the regulatory mechanisms employed by them.
PubMed: 32010617
DOI: 10.3389/fonc.2019.01516 -
American Journal of Cancer Research 2021Inflammatory mediators in tumor microenvironment influence cancer occurrence, growth and metastasis through complex signaling networks. Excessive inflammation is closely... (Review)
Review
Inflammatory mediators in tumor microenvironment influence cancer occurrence, growth and metastasis through complex signaling networks. Excessive inflammation is closely associated with elevated cancer risk and mortality, in part through inflammation-induced angiogenesis. Mechanistically, multiple tumor-associated inflammatory cells increase the release and accumulation of various inflammatory products in cancerous sites. These products in turn activate tumor associated signaling cascades such as STAT3, NF-κB, PI3K/Akt and p38 MAPK, which mediate the recruitment of inflammatory cells and secretion of pro-inflammatory factors. More importantly, these events promote the secretion of various pro-angiogenesis factors from endothelial, tumor and inflammatory cells, which then drive malignancy in endothelial cells in a paracrine and/or autocrine manner. Its ultimate effect is to promote endothelial cell proliferation, migration, survival and tube formation, and to hence the formation of blood vessels in tumors. This review describes the signaling network that connects the interaction between inflammation and cancer, especially those involved in inflammation-induced angiogenesis. This will reveal potential targets for the design of anti-inflammatory treatments and drugs that inhibites tumor growth and angiogenesis.
PubMed: 33575073
DOI: No ID Found -
Vascular Biology (Bristol, England) 2019PI3Ks belong to a family of lipid kinases that comprises eight isoforms. They phosphorylate the third position of the inositol ring present in phosphatidylinositol... (Review)
Review
PI3Ks belong to a family of lipid kinases that comprises eight isoforms. They phosphorylate the third position of the inositol ring present in phosphatidylinositol lipids and, in turn, activate a broad range of proteins. The PI3K pathway regulates primal cellular responses, including proliferation, migration, metabolism and vesicular traffic. These processes are fundamental for endothelial cell function during sprouting angiogenesis, the most common type of blood vessel formation. Research in animal models has revealed key functions of PI3K family members and downstream effectors in angiogenesis. In addition, perturbations in PI3K signalling have been associated with aberrant vascular growth including tumour angiogenesis and vascular malformations. Together, this highlights that endothelial cells are uniquely sensitive to fluctuations in PI3K signalling. Here, we aim to update the current view on this important signalling cue in physiological and pathological blood vessel growth.
PubMed: 32923964
DOI: 10.1530/VB-19-0025 -
Biomedicine & Pharmacotherapy =... Dec 2022Over the last few decades, our understanding of the molecular mechanisms underlying tumor angiogenesis has advanced at a significant pace and the clinical translation of... (Review)
Review
Over the last few decades, our understanding of the molecular mechanisms underlying tumor angiogenesis has advanced at a significant pace and the clinical translation of these mechanisms has benefited millions of patients. However, limited efficacy and the rapid expansion of drug resistance remain unresolved issues. Recent studies in both preclinical and clinical settings have revealed that circRNAs, as a novel identified non-coding RNA can mediate intercellular communication and regulate the microenvironment within tumors after being selectively packaged, secreted, and transmitted via exosomes. This review aims to provide a comprehensive understanding of how exosomal circRNAs orchestrate inducers and inhibitors of angiogenesis, including their functions, molecular mechanisms, and potential roles as diagnostic biomarkers and therapeutic targets. Finally, we discuss the technological advances in exosome functionalization and exosome-mimetic nanovesicles intending to improve the clinical translation of exosomal circRNAs.
Topics: Humans; RNA, Circular; Neovascularization, Pathologic; Exosomes; Neoplasms; Cell Communication; Tumor Microenvironment
PubMed: 36411614
DOI: 10.1016/j.biopha.2022.113921 -
International Journal of Molecular... Nov 2022Platelets are an active component of the tumor microenvironment (TME), involved in the regulation of multiple tumor processes, including angiogenesis. They are generated... (Review)
Review
Platelets are an active component of the tumor microenvironment (TME), involved in the regulation of multiple tumor processes, including angiogenesis. They are generated rich in angiogenic factors in their granules to actively participate in the hemostatic process by megakaryocytes and further enriched in angiogenic factors by all components of the tumor microenvironment to control the angiogenic process because of their preferential relationship with the endothelial component of vessels. In recent decades, the literature has reported a great deal of evidence on the role of platelets in tumor angiogenesis; however, it is unclear whether the number or mean volume of platelets and/or their content and localization in TME may have clinical relevance in the choice and management of therapy for the cancer patient. In this scoping review, we collected and critically reviewed the scientific evidence supporting a close relationship between platelets, cancer, and angiogenesis. The aim of this work was to define the landscape of platelet-activated angiogenesis in cancer progression and analyze what and how much evidence is present in the last 20 years in the literature at both the preclinical and clinical levels, to answer whether platelets could be a useful determinant for analyzing tumor angiogenesis. In conclusion, this scoping review indicates that there is much evidence, both preclinical and clinical, but in the preclinical context, studies demonstrate the direct involvement of platelets in tumor angiogenesis; in the clinical context the evidence is indirect, though strong, and the indication of how and to what extent platelet content contributes to tumor angiogenesis is lacking. So, do we need more evidence or better analysis? More molecular and quali-quantitative data is needed to translate the results obtained in preclinical studies into the clinical setting. This information about platelets, if correlated with tumor type and its biology, including tumor vasculature, type of angiogenesis, and patient characteristics (age, sex, comorbidities, drug treatments for chronic diseases) could be an important pa- rameter for correlating platelet biology to angiogenesis, for personalizing cancer therapy, and for clinical prognosis.
Topics: Humans; Blood Platelets; Neovascularization, Pathologic; Neoplasms; Tumor Microenvironment
PubMed: 36362186
DOI: 10.3390/ijms232113401 -
Scientific Reports Nov 2020Angiogenesis is a physiological process for the formation of new blood vessels from the pre-existing vessels and it has a vital role in the survival and growth of...
Angiogenesis is a physiological process for the formation of new blood vessels from the pre-existing vessels and it has a vital role in the survival and growth of neoplasms. During tumor angiogenesis, the activation of the gene transcriptions in vascular endothelial cells (ECs) plays an essential role in the promotion of EC proliferation, migration, and vascular network development. However, the molecular mechanisms underlying transcriptional regulation of EC and tumor angiogenesis remains to be fully elucidated. Here we report that the transcription factor Yin Yang 1 (YY1) in ECs is critically involved in tumor angiogenesis. First, we utilized a tamoxifen-inducible EC-specific YY1 deficient mouse model and showed that YY1 deletion in ECs inhibited the tumor growth and tumor angiogenesis. Using the in vivo matrigel plug assay, we then found that EC-specific YY1 ablation inhibited growth factor-induced angiogenesis. Furthermore, vascular endothelial growth factor (VEGF)-induced EC migration was diminished in YY1-depleted human umbilical vein endothelial cells (HUVECs). Finally, a rescue experiment revealed that YY1-regulated BMP6 expression in ECs was involved in EC migration. Collectively, our results demonstrate that endothelial YY1 has a crucial role in tumor angiogenesis and suggest that targeting endothelial YY1 could be a potential therapeutic strategy for cancer treatment.
Topics: Animals; Cell Movement; Cell Proliferation; Collagen; Drug Combinations; Endothelial Cells; Gene Deletion; Gene Expression Regulation, Neoplastic; Human Umbilical Vein Endothelial Cells; Humans; Laminin; Melanoma; Mice, Knockout; Neovascularization, Pathologic; Proteoglycans; RNA, Small Interfering; Vascular Endothelial Growth Factor A; YY1 Transcription Factor
PubMed: 33235311
DOI: 10.1038/s41598-020-77568-z -
CA: a Cancer Journal For Clinicians 1972
Topics: Blood Vessels; Neoplasms
PubMed: 4625047
DOI: 10.3322/canjclin.22.4.226