-
Molecular Therapy. Nucleic Acids Mar 2022Exosomes are extracellular vesicles released by various cell types that perform various biological functions, mainly mediating communication between different cells,... (Review)
Review
Exosomes are extracellular vesicles released by various cell types that perform various biological functions, mainly mediating communication between different cells, especially those active in cancer. Noncoding RNAs (ncRNAs), of which there are many types, were recently identified as enriched and stable in the exocrine region and play various roles in the occurrence and progression of cancer. Abnormal angiogenesis has been confirmed to be related to human cancer. An increasing number of studies have shown that exosome-derived ncRNAs play an important role in tumor angiogenesis. In this review, we briefly outline the characteristics of exosomes, ncRNAs, and tumor angiogenesis. Then, the mechanism of the impact of exosome-derived ncRNAs on tumor angiogenesis is analyzed from various angles. In addition, we focus on the regulatory role of exosome-derived ncRNAs in angiogenesis in different types of cancer. Furthermore, we emphasize the potential role of exosome-derived ncRNAs as biomarkers in cancer diagnosis and prognosis and therapeutic targets in the treatment of tumors.
PubMed: 35317280
DOI: 10.1016/j.omtn.2022.01.009 -
Oncotarget Jul 2017Angiogenesis is crucial for tumor growth and metastasis. Cadmium (Cd) exposure is associated with elevated cancer risk and mortality. Such association is, at least in... (Review)
Review
Angiogenesis is crucial for tumor growth and metastasis. Cadmium (Cd) exposure is associated with elevated cancer risk and mortality. Such association is, at least in part, attributable to Cd-induced tumor angiogenesis. Nevertheless, the reported effects of Cd on tumor angiogenesis appear to be either stimulatory or inhibitory, depending on the concentrations. Ultra-low concentrations of Cd (<0.5 μM) inhibit endothelial nitric oxide synthase activation, leading to reduced endothelial nitric oxide production and attenuated tumor angiogenesis. In contrast, low-lose Cd (1-10 μM) up-regulates vascular endothelial growth factor (VEGF)-mediated tumor angiogenesis by exerting sub-apoptotic levels of oxidative stress on both tumor cells and endothelial cells (ECs). The consequent activation of protein kinase B/Akt, nuclear factor-κB, and mitogen-activated protein kinase signaling cascades mediate the increased secretion of VEGF by tumor cells and the up-regulated VEGF receptor-2 expression in ECs. Furthermore, Cd in high concentrations (>10 μM) induces EC apoptosis via the activation of caspase-3, resulting in destruction of tumor vasculature. In this review, we summarize the current knowledge concerning the roles of Cd in tumor angiogenesis, with a focus on molecular mechanisms underlying the dose dependent effects of Cd on various EC phenotypes.
Topics: Animals; Cadmium; Dose-Response Relationship, Drug; Endothelial Cells; Environmental Pollutants; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; Neovascularization, Pathologic; Nitric Oxide Synthase Type III; Oxidative Stress; Proto-Oncogene Proteins c-akt; Signal Transduction; Vascular Endothelial Growth Factor A
PubMed: 28388546
DOI: 10.18632/oncotarget.16572 -
PPAR Research 2020PPARs are ligand-activated transcriptional factors that belong to the nuclear receptor superfamily. Among them, PPAR alpha and PPAR gamma are prone to exert an... (Review)
Review
PPARs are ligand-activated transcriptional factors that belong to the nuclear receptor superfamily. Among them, PPAR alpha and PPAR gamma are prone to exert an antiangiogenic effect, whereas PPAR beta/delta has an opposite effect in physiological and pathological conditions. Angiogenesis has been known as a hallmark of cancer, and our recent works also demonstrate that vascular-specific PPAR beta/delta overexpression promotes tumor angiogenesis and progression in vivo. In this review, we will mainly focus on the role of PPAR beta/delta in tumor angiogenesis linked to the tumor microenvironment to further facilitate tumor progression and metastasis. Moreover, the crosstalk between PPAR beta/delta and its downstream key signal molecules involved in tumor angiogenesis will also be discussed, and the network of interplay between them will further be established in the review.
PubMed: 32855630
DOI: 10.1155/2020/3608315 -
Bulletin Du Cancer May 2003Recent advances in the understanding of the molecular control of angiogenesis have shown that this process is essential for tumor development and spread. The... (Review)
Review
Recent advances in the understanding of the molecular control of angiogenesis have shown that this process is essential for tumor development and spread. The identification of a great many of ligands, receptors or intracellular signalling molecules have allowed to unravel some of the regulatory loops involved. Especially noteworthy is the fact that developmental regulators seem now to play a role in tumor angiogenesis. Furthermore, these studies have allowed to identify novel therapeutic targets and to develop novel molecules and strategies for cancer therapy. This indicates that tumor angiogenesis is at present a major focus of cancer research.
Topics: Angiogenesis Inhibitors; Growth Substances; Humans; Neoplasms; Neovascularization, Pathologic; Signal Transduction
PubMed: 12850768
DOI: No ID Found -
Molecular Cancer Feb 2018Angiogenesis is essential for tumor growth and metastasis. Understanding the regulation of tumor angiogenesis has become increasingly important. MicroRNAs (miRNAs) are... (Review)
Review
Angiogenesis is essential for tumor growth and metastasis. Understanding the regulation of tumor angiogenesis has become increasingly important. MicroRNAs (miRNAs) are small noncoding RNAs that function in diverse biological processes via post-transcriptional regulation. Extensive studies have revealed two important regulatory roles of miRNAs in tumor angiogenesis: miRNAs in tumor cells affect the activity of endothelial cells via non-cell-autonomous mechanisms, and miRNAs in endothelial cells regulate the cell-autonomous behavior. Recent advances have further highlighted the role of tumor-derived extracellular vesicles in the regulation of tumor angiogenesis via transferring miRNAs to endothelial cells. In this review, we summarize the regulatory role of miRNA in tumor angiogenesis, with a highlight on clinical implications of miRNAs as biomarkers for anti-angiogenic therapy response, and as therapeutic interventions against tumor angiogenesis in vivo.
Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Biomarkers; Endothelial Cells; Extracellular Vesicles; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Molecular Targeted Therapy; Neoplasms; Neovascularization, Pathologic; RNA; RNA Interference; RNA, Circular; Treatment Outcome; Vascular Endothelial Growth Factor A
PubMed: 29415727
DOI: 10.1186/s12943-018-0766-4 -
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 -
Cellular and Molecular Life Sciences :... Feb 2017VEGF-driven tumor angiogenesis has been validated as a central target in several tumor types deserving of continuous and further considerations to improve the efficacy... (Review)
Review
VEGF-driven tumor angiogenesis has been validated as a central target in several tumor types deserving of continuous and further considerations to improve the efficacy and selectivity of the current therapeutic paradigms. Epsins, a family of endocytic clathrin adaptors, have been implicated in regulating endothelial cell VEGFR2 signaling, where its inactivation leads to nonproductive leaky neo-angiogenesis and, therefore, impedes tumor development and progression. Targeting endothelial epsins is of special significance due to its lack of affecting other angiogenic-signaling pathways or disrupting normal quiescent vessels, suggesting a selective modulation of tumor angiogenesis. This review highlights seminal findings on the critical role of endothelial epsins in tumor angiogenesis and their underlying molecular events, as well as strategies to prohibit the normal function of endogenous endothelial epsins that capitalize on these newly understood mechanisms.
Topics: Adaptor Proteins, Vesicular Transport; Angiogenesis Inhibitors; Animals; Drug Discovery; Endothelium; Humans; Molecular Targeted Therapy; Neoplasms; Neovascularization, Pathologic; Signal Transduction; Vascular Endothelial Growth Factor Receptor-2
PubMed: 27572288
DOI: 10.1007/s00018-016-2347-2 -
Medecine Sciences : M/S Nov 2015Angiogenesis is a highly controlled multistep process that allows the formation of a harmonious vascular network during embryonic development and in adults. In addition,... (Review)
Review
Angiogenesis is a highly controlled multistep process that allows the formation of a harmonious vascular network during embryonic development and in adults. In addition, tumor progression also involves a dedicated blood vessel supply to fuel the tumor mass, pirating physiological molecular and cellular mechanisms. However, tumor angiogenesis is a quite inefficient process, as perfusion is not optimal, vessel integrity is not guaranteed, and vessel network is irrationally organized. While fundamental molecular and cellular mechanisms have been the field of intense investigation, anticancer therapies have evolved with the possibility to target tumor angiogenesis. This review presents the different steps involved in the formation of normal and tumor angiogenesis, and how tumor vasculature abnormalities could contribute to tumorigenesis and conventional therapy failure.
Topics: Adult; Animals; Cell Fusion; Cell Movement; Humans; Neoplasms; Neovascularization, Pathologic; Neovascularization, Physiologic; Regional Blood Flow
PubMed: 26576606
DOI: 10.1051/medsci/20153111013 -
Frontiers in Cell and Developmental... 2021Angiogenesis is required for tumor growth and development. Extracellular vesicles (EVs) are important signaling entities that mediate communication between diverse types... (Review)
Review
Angiogenesis is required for tumor growth and development. Extracellular vesicles (EVs) are important signaling entities that mediate communication between diverse types of cells and regulate various cell biological processes, including angiogenesis. Recently, emerging evidence has suggested that tumor-derived EVs play essential roles in tumor progression by regulating angiogenesis. Thousands of molecules are carried by EVs, and the two major types of biomolecules, noncoding RNAs (ncRNAs) and proteins, are transported between cells and regulate physiological and pathological functions in recipient cells. Understanding the regulation of EVs and their cargoes in tumor angiogenesis has become increasingly important. In this review, we summarize the effects of tumor-derived EVs and their cargoes, especially ncRNAs and proteins, on tumor angiogenesis and their mechanisms, and we highlight the clinical implications of EVs in bodily fluids as biomarkers and as diagnostic, prognostic, and therapeutic targets in cancer patients.
PubMed: 34966744
DOI: 10.3389/fcell.2021.791882 -
Journal of Molecular and Cellular... Feb 2011Contribution from diverse tissue-specific stem cell types is required to create the cell populations necessary for the activation of angiogenesis and neovascular growth... (Review)
Review
Contribution from diverse tissue-specific stem cell types is required to create the cell populations necessary for the activation of angiogenesis and neovascular growth in cancer. Bone marrow (BM)-derived circulating endothelial progenitors (EPCs) that would differentiate to bona fide endothelial cells (ECs) were previously believed to be necessary for tumor angiogenesis. However, numerous recent studies demonstrate that EPCs are not needed for tumor angiogenesis and indicate EPCs to be artifactual rather than physiological. It is evident that tumor infiltrating hematopoietic cells produced by BM-residing hematopoietic stem cells (HSCs) may contribute to tumor angiogenesis in a paracrine manner by stimulating ECs or by remodeling the extracellular matrix. Therefore, identification of the various hematopoietic cell subpopulations that are critical for tumor angiogenesis and better understanding of their proangiogenic functions and mechanisms of action have potential therapeutic significance. Stem and progenitor cell subsets for also other vascular or perivascular cell types such as pericytes or mesenchymal/stromal cells may provide critical contributions to the growing neovasculature. Furthermore, we hypothesize that the existence of a yet undiscovered-and largely unsearched-tissue-specific adult vascular endothelial stem cell (VESC) would provide completely novel targeted approaches to block pathological angiogenesis and cancer growth. This article is part of a special issue entitled, "Cardiovascular Stem Cells Revisited".
Topics: Animals; Cell Differentiation; Endothelial Cells; Hematopoietic Stem Cells; Humans; Mesenchymal Stem Cells; Neoplasms; Neovascularization, Pathologic; Paracrine Communication; Pericytes; Stem Cells
PubMed: 21047516
DOI: 10.1016/j.yjmcc.2010.10.024