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Cells Mar 2022Extracellular vesicles (EVs) act as multifunctional regulators of intercellular communication and are involved in diverse tumor phenotypes, including tumor angiogenesis,... (Review)
Review
Extracellular vesicles (EVs) act as multifunctional regulators of intercellular communication and are involved in diverse tumor phenotypes, including tumor angiogenesis, which is a highly regulated multi-step process for the formation of new blood vessels that contribute to tumor proliferation. EVs induce malignant transformation of distinct cells by transferring DNAs, proteins, lipids, and RNAs, including noncoding RNAs (ncRNAs). However, the functional relevance of EV-derived ncRNAs in tumor angiogenesis remains to be elucidated. In this review, we summarized current research progress on the biological functions and underlying mechanisms of EV-derived ncRNAs in tumor angiogenesis in various cancers. In addition, we comprehensively discussed the potential applications of EV-derived ncRNAs as cancer biomarkers and novel therapeutic targets to tailor anti-angiogenic therapy.
Topics: Biomarkers, Tumor; Extracellular Vesicles; Humans; Neoplasms; Neovascularization, Pathologic; RNA, Untranslated
PubMed: 35326397
DOI: 10.3390/cells11060947 -
International Journal of Molecular... Jul 2020The tumor vasculature is essential for tumor growth and metastasis, and is a prime target of several anti-cancer agents. Increasing evidence indicates that tumor... (Review)
Review
The tumor vasculature is essential for tumor growth and metastasis, and is a prime target of several anti-cancer agents. Increasing evidence indicates that tumor angiogenesis is stimulated by extracellular vesicles (EVs) that are secreted or shed by cancer cells. These EVs encapsulate a variety of biomolecules with angiogenic properties, and have been largely thought to stimulate vessel formation by transferring this luminal cargo into endothelial cells. However, recent studies have revealed that EVs can also signal to recipient cells via proteins on the vesicular surface. This review discusses and integrates emerging insights into the diverse mechanisms by which proteins associate with the EV membrane, the biological functions of EV membrane-associated proteins in tumor angiogenesis, and the clinical significance of these proteins in anti-angiogenic therapy.
Topics: Angiogenesis Inhibitors; Angiogenic Proteins; Drug Resistance, Neoplasm; Extracellular Vesicles; Humans; Membrane Proteins; Neoplasms; Neovascularization, Pathologic
PubMed: 32751440
DOI: 10.3390/ijms21155418 -
International Journal of Molecular... Dec 2017Glioblastoma (GBM) is considered one of the most malignant, genetically heterogeneous, and therapy-resistant solid tumor. Therapeutic options are limited in GBM and... (Review)
Review
Glioblastoma (GBM) is considered one of the most malignant, genetically heterogeneous, and therapy-resistant solid tumor. Therapeutic options are limited in GBM and involve surgical resection followed by chemotherapy and/or radiotherapy. Adjuvant therapies, including antiangiogenic treatments (AATs) targeting the VEGF-VEGFR pathway, have witnessed enhanced infiltration of bone marrow-derived myeloid cells, causing therapy resistance and tumor relapse in clinics and in preclinical models of GBM. This review article is focused on gathering previous clinical and preclinical reports featuring major challenges and lessons in GBM. Potential combination therapies targeting the tumor microenvironment (TME) to overcome the myeloid cell-mediated resistance problem in GBM are discussed. Future directions are focused on the use of TME-directed therapies in combination with standard therapy in clinical trials, and the exploration of novel therapies and GBM models for preclinical studies. We believe this review will guide the future of GBM research and therapy.
Topics: Angiogenesis Inhibitors; Glioblastoma; Humans; Myeloid Cells; Neovascularization, Pathologic; Tumor Microenvironment
PubMed: 29258180
DOI: 10.3390/ijms18122732 -
Journal of Translational Medicine Jun 2020Angiogenesis is a multistep process and various molecules are involved in regulating it. Extracellular vesicles are cell-derived particles, secreted from several types... (Review)
Review
Angiogenesis is a multistep process and various molecules are involved in regulating it. Extracellular vesicles are cell-derived particles, secreted from several types of cells and are known to mediate cell-to-cell communication. These vesicles contain different bio-molecules including nucleic acids, proteins, and lipids, which are transported between cells and regulate physiological and pathological conditions in the recipient cell. Exosomes, 30-150 nm extracellular vesicles, and their key roles in tumorigenesis via promoting angiogenesis are of great recent interest. In solid tumors, the suitable blood supply is the hallmark of their progression, growth, and metastasis, so it can be supported by angiogenesis. Tumor cells abundantly release exosomes containing different kinds of biomolecules such as angiogenic molecules that contribute to inducing angiogenesis. These exosomes can be trafficked between tumor cells or between tumor cells and endothelial cells. The protein and nucleic acid cargo of tumor derived-exosomes can deliver to endothelial cells mostly by endocytosis, and then induce angiogenesis. Tumor derived-exosomes can be used as biomarker for cancer diagnosis. Targeting exosome-induced angiogenesis may serve as a promising tool for cancer therapy. Taken together, tumor derived-exosomes are the major contributors in tumor angiogenesis and a supposed target for antiangiogenic therapies. However, further scrutiny is essential to investigate the function of exosomes in tumor angiogenesis and clinical relevance of targeting exosomes for suppressing angiogenesis.
Topics: Cell Communication; Endothelial Cells; Exosomes; Humans; Neoplasms; Neovascularization, Pathologic
PubMed: 32571337
DOI: 10.1186/s12967-020-02426-5 -
British Journal of Cancer Jan 2006The angiogenic activity of peptide adrenomedullin (AM) was first shown in 1998 . Since then, a number of reports have confirmed the ability of AM to induce the growth... (Review)
Review
The angiogenic activity of peptide adrenomedullin (AM) was first shown in 1998 . Since then, a number of reports have confirmed the ability of AM to induce the growth and migration of isolated vascular endothelial and smooth muscle cells in vitro and to promote angiogenesis in xenografted tumours in vivo. In addition, knockout murine models point to an essential role for AM in embryonic vasculogenesis and ischaemic revascularisation. AM expression is upregulated by hypoxia (a typical feature of solid tumours) and a potential role as a regulator of carcinogenesis and tumour progression has been proposed based on studies in vitro and in animal models. Nevertheless, translational research on AM, and in particular, confirmation of its importance in the vascularisation of human tumours has lagged behind. In this commentary, we review current progress and potential directions for future research into the role of AM in tumour angiogenesis.
Topics: Adrenomedullin; Animals; Cell Hypoxia; Cell Transformation, Neoplastic; Disease Models, Animal; Gene Expression Regulation; Humans; Neoplasms; Neovascularization, Pathologic; Peptides; Signal Transduction; Transplantation, Heterologous
PubMed: 16251875
DOI: 10.1038/sj.bjc.6602832 -
Recent Patents on Anti-cancer Drug... 2018Massive vessel recruitment is required to sustain rapid tumor growth by delivering oxygen and nutrients. Current strategies to counteract angiogenesis are mostly aimed... (Review)
Review
BACKGROUND
Massive vessel recruitment is required to sustain rapid tumor growth by delivering oxygen and nutrients. Current strategies to counteract angiogenesis are mostly aimed at reducing tumor vessel density. However, many of these drugs have been shown to trigger hypoxia, thus exacerbating tumor aggressiveness. Promising results come from a completely different approach based on the "normalization" of the endothelial layer and the consequent improvement of the vascular function. This new strategy would ameliorate drug delivery to the tumor meanwhile reducing invasiveness and metastatisation.
OBJECTIVE
Since endothelial metabolism has proved essential in the regulation of the angiogenic switch, many recent patents focus on agents able to inhibit specific metabolic pathways in Tumor- Associated Endothelial Cells (TECs) in order to provide vessel normalization. Here, we provide a review of the recent advances in the development of patents on agents targeting endothelial metabolism that have proved effective in several vascular disorders.
METHODS
Results of genetic and pharmacologic studies that brought to the development of patents for methods to counteract aberrant angiogenesis were analysed and sub-divided according to the specific metabolic pathway targeted.
RESULTS
Growing evidences indicate that targeting specific molecular players involved in the endothelial metabolic remodelling required to sustain aberrant angiogenesis, is a valuable therapeutic strategy that can be exploited in vascular disorders as well as in tumor angiogenesis.
CONCLUSION
These findings might have important implications in clinics and could be particularly relevant to patients developing resistance to traditional anti-angiogenic drugs.
Topics: Angiogenesis Inhibitors; Animals; Drug Delivery Systems; Humans; Neoplasms; Neovascularization, Pathologic; Patents as Topic
PubMed: 29807523
DOI: 10.2174/1574892813666180528105023 -
Frontiers in Bioscience (Landmark... Jun 2009Transforming growth factor-beta (TGF-beta) family members are secreted multifunctional cytokines that play pivotal roles in development and disease. The prototypic... (Review)
Review
Transforming growth factor-beta (TGF-beta) family members are secreted multifunctional cytokines that play pivotal roles in development and disease. The prototypic member of this family, TGF-beta, plays a dual role in carcinogenesis, acting as a tumor suppressor in early stages and as tumor promoter in late stages of tumor progression. Numerous studies support the notion that pathological angiogenesis is one of the hallmarks of cancer. Tumor angiogenesis is regulated by a network of growth factors, including members of the TGF-beta family. TGF-beta acts in a context-dependent manner and can either stimulate or inhibit tumor angiogenesis. In this review, we discuss our current understanding on how TGF-beta family members affect endothelial and smooth muscle cell function and how perturbed TGF-beta signaling may contribute to tumor angiogenesis and tumor progression.
Topics: Animals; Bone Morphogenetic Proteins; Endothelial Cells; Humans; Intracellular Signaling Peptides and Proteins; Models, Biological; Myocytes, Smooth Muscle; Neoplasms; Neovascularization, Pathologic; Signal Transduction; Smad Proteins; Transforming Growth Factor beta
PubMed: 19482591
DOI: 10.2741/3573 -
Oncology Reports Aug 2020Tumor angiogenesis is a hallmark of liver cancer and is necessary for tumor growth and progression. Supervillin (SVIL) is highly expressed and implicated in several...
Tumor angiogenesis is a hallmark of liver cancer and is necessary for tumor growth and progression. Supervillin (SVIL) is highly expressed and implicated in several malignant processes of liver cancer. However, the functional relationships between SVIL and tumor angiogenesis in liver cancer have not yet been fully elucidated. The present study was based on bioinformatics analysis, patient tissue sample detection, three‑dimensional simulated blood vessel formation, a series of cytological experiments and mouse models. The results demonstrated the important role of SVIL in the progression of malignant liver cancer and tumor angiogenesis, both in terms of vasculogenic mimicry (VM) and endothelium‑dependent vessel (EDV) development. SVIL knockdown inhibited VM formation and induced tumor cell apoptosis via the VEGF‑p38 signaling axis and through various VM‑associated transcriptional factors, including vascular endothelial‑cadherin, matrix metalloproteinase 9/12 and migration‑inducing protein 7. SVIL may therefore be considered a potential tumor vascular biomarker and a promising therapeutic target for patients with liver cancer.
Topics: Animals; Cell Movement; Cell Survival; Gene Expression Regulation, Neoplastic; Hep G2 Cells; Human Umbilical Vein Endothelial Cells; Humans; Liver Neoplasms; MAP Kinase Signaling System; Male; Membrane Proteins; Mice; Microfilament Proteins; Neoplasm Transplantation; Up-Regulation; Vascular Endothelial Growth Factor A
PubMed: 32468064
DOI: 10.3892/or.2020.7621 -
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 -
Cancer Drug Resistance (Alhambra,... 2020Cancer is the second leading cause of death worldwide. The survival of cancer patients depends on the efficacy of therapies and the development of resistance. There are... (Review)
Review
Cancer is the second leading cause of death worldwide. The survival of cancer patients depends on the efficacy of therapies and the development of resistance. There are many mechanisms involved in the acquisition of drug resistance by cancer cells, including the acquisition of stem-like features. Cancer stem cells (CSCs) represent a major source of tumor progression and treatment resistance. CSCs are a subpopulation of cancer cells having the abilities to self-renew and form spheres . Aldehyde dehydrogenase 1A1 (ALDH1A1) is a cytosolic enzyme involved in the detoxification of cells from toxic aldehydes and belongs to the ALDH family. High ALDH1A1 activity is closely related to stemness phenotype of several tumors, possibly contributing to cancer progression and diffusion in the body. We have documented the contribution of ALDH1A1 in tumor angiogenesis in breast cancer cells by the activation of hypoxia inducible factor-1α and vascular endothelial growth factor signaling. This review discusses the involvement of ALDH1A1 in the development of different hallmarks of cancer to propose it as a novel putative target for cancer treatment to achieve better outcome. Here, we analyze the involvement of ALDH1A1 in the acquisition of stemness phenotype in tumor cells, the regulation of tumor angiogenesis and metastases, and the acquisition of anticancer drug resistance and immune evasion.
PubMed: 35582039
DOI: 10.20517/cdr.2019.70