-
International Journal of Molecular... Dec 2016Integrins are heterodimeric cell surface receptors that bind to different extracellular ligands depending on their composition and regulate all processes which enable... (Review)
Review
Integrins are heterodimeric cell surface receptors that bind to different extracellular ligands depending on their composition and regulate all processes which enable multicellular life. In cancer, integrins trigger and play key roles in all the features that were once described as the . In this review, we will discuss the contribution of integrins to these hallmarks, including uncontrolled and limitless proliferation, invasion of tumor cells, promotion of tumor angiogenesis and evasion of apoptosis and resistance to growth suppressors, by highlighting the latest findings. Further on, given the paramount role of integrins in cancer, we will present novel strategies for integrin inhibition that are starting to emerge, promising a hopeful future regarding cancer treatment.
Topics: Animals; Apoptosis; Humans; Integrins; Neoplasms; Neovascularization, Pathologic; Signal Transduction
PubMed: 27929432
DOI: 10.3390/ijms17122037 -
Human Vaccines Sep 2011Tumors stimulate angiogenesis to meet increasing nutrient and oxygen demands. In addition to their role in vascular remodeling, pro-angiogenic cytokines and effector...
Tumors stimulate angiogenesis to meet increasing nutrient and oxygen demands. In addition to their role in vascular remodeling, pro-angiogenic cytokines and effector cells contribute to an immune-inhibitory environment associated with advanced malignancies. Despite the critical role of angiogenesis in tumor growth and dissemination, most anti-angiogenic cancer therapies have had only limited success selectively targeting one of the many factors implicated in this process. Similarly, the effectiveness of tumor immunotherapies has been limited by tumor-mediated escape mechanisms and immune suppression. By combining the two strategies, however, anti-angiogenic immunotherapy offers the possibility to more robustly inhibit tumor angiogenesis and simultaneously impact the immune-inhibitory effects of the pro-angiogenic tumor milieu. These potential synergies make the combination of immunotherapy and anti-angiogenic treatment a promising avenue for future research.
Topics: Angiogenesis Inhibitors; Animals; Cancer Vaccines; Humans; Immunotherapy; Neoplasms; Neovascularization, Pathologic
PubMed: 21860259
DOI: 10.4161/hv.7.9.16407 -
Cellular and Molecular Life Sciences :... Mar 2008The thrombospondins (TSPs) are a family of five proteins that are involved in the tissue remodeling that is associated with embryonic development, wound healing,... (Review)
Review
The thrombospondins (TSPs) are a family of five proteins that are involved in the tissue remodeling that is associated with embryonic development, wound healing, synaptogenesis, and neoplasia. These proteins mediate the interaction of normal and neoplastic cells with the extracellular matrix and surrounding tissue. In the tumor microenvironment, TSP-1 has been shown to suppress tumor growth by inhibiting angiogenesis and by activating transforming growth factor beta. TSP-1 inhibits angiogenesis through direct effects on endothelial cell migration and survival, and through effects on vascular endothelial cell growth factor bioavailability. In addition, TSP-1 may affect tumor cell function through interaction with cell surface receptors and regulation of extracellular proteases. Whereas the role of TSP-1 in the tumor microenvironment is the best characterized, the other TSPs may have similar functions. (Part of a Multi-author Review).
Topics: Angiogenesis Inhibitors; Animals; Humans; Neoplasms; Neovascularization, Pathologic; Thrombospondin 1
PubMed: 18193162
DOI: 10.1007/s00018-007-7486-z -
Microcirculation (New York, N.Y. : 1994) Jan 2014Ample interest has been evoked in using placental angiogenesis as a target for the development of diagnosis tools and potential therapeutics for pregnancy complications... (Review)
Review
Ample interest has been evoked in using placental angiogenesis as a target for the development of diagnosis tools and potential therapeutics for pregnancy complications based on the knowledge of placental angiogenesis in normal and aberrant pregnancies. Although these goals are still far from reach, one would expect that two complementary processes should be balanced for therapeutic angiogenesis to be successful in restoring a mature and functional vascular network in the placenta in any pregnancy complication: (i) pro-angiogenic stimulation of new vessel growth and (ii) anti-angiogenic inhibition of vessel overgrowth. As the best model of physiological angiogenesis, investigations of placental angiogenesis provide critical insights not only for better understanding of normal placental endothelial biology but also for the development of diagnosis tools for pregnancy complications. Such investigations will potentially identify novel pro-angiogenic factors for therapeutic intervention for tissue damage in various obstetric complications or heart failure or anti-angiogenic factors to target on cancer or vision loss in which circulation needs to be constrained. This review summarizes the genetic and molecular aspects of normal placental angiogenesis as well as the signaling mechanisms by which the dominant angiogenic factor vascular endothelial growth factor regulates placental angiogenesis with a focus on placental endothelial cells.
Topics: Endothelial Cells; Female; Humans; Neovascularization, Pathologic; Neovascularization, Physiologic; Placenta; Pregnancy; Vascular Endothelial Growth Factor A
PubMed: 23981199
DOI: 10.1111/micc.12093 -
Cellular and Molecular Life Sciences :... Jun 2022All living beings continue their life by receiving energy and by excreting waste products. In animals, the arteries are the pathways of these transfers to the cells.... (Review)
Review
All living beings continue their life by receiving energy and by excreting waste products. In animals, the arteries are the pathways of these transfers to the cells. Angiogenesis, the formation of the arteries by the development of pre-existed parental blood vessels, is a phenomenon that occurs naturally during puberty due to certain physiological processes such as menstruation, wound healing, or the adaptation of athletes' bodies during exercise. Nonetheless, the same life-giving process also occurs frequently in some patients and, conversely, occurs slowly in some physiological problems, such as cancer and diabetes, so inhibiting angiogenesis has been considered to be one of the important strategies to fight these diseases. Accordingly, in tissue engineering and regenerative medicine, the highly controlled process of angiogenesis is very important in tissue repairing. Excessive angiogenesis can promote tumor progression and lack of enough angiogensis can hinder tissue repair. Thereby, both excessive and deficient angiogenesis can be problematic, this review article introduces and describes the types of factors involved in controlling angiogenesis. Considering all of the existing strategies, we will try to lay out the latest knowledge that deals with stimulating/inhibiting the angiogenesis. At the end of the article, owing to the early-reviewed mechanical aspects that overshadow angiogenesis, the strategies of angiogenesis in tissue engineering will be discussed.
Topics: Animals; Humans; Neovascularization, Pathologic; Neovascularization, Physiologic; Regenerative Medicine; Tissue Engineering; Wound Healing
PubMed: 35672585
DOI: 10.1007/s00018-022-04348-5 -
Cancer Treatment and Research... 2021Angiogenesis plays an important role in the development of cancer since it allows for the delivery of oxygen, nutrients, and growth factors as well as tumor... (Review)
Review
Angiogenesis plays an important role in the development of cancer since it allows for the delivery of oxygen, nutrients, and growth factors as well as tumor dissemination to distant organs. Inhibition of angiogenesis is an important strategy for the prevention of multiple solid tumors that depend on cutting or at least reducing the blood supply to tumor micro-regions, resulting in pan-hypoxia and pan-necrosis within solid tumor tissues. These drugs are an important part of treatment for some types of cancer. As a stand-alone therapy, inhibition of tumor angiogenesis can arrest or halt tumor growth, but will not eliminate the tumor. Therefore, anti-angiogenic drugs in combinations with another anti-cancer treatment method, like chemotherapy, lead to being critical for optimum cancer patient outcomes. Over the last two decades, investigations have been made to improve the efficacy of anti-angiogenic drugs, recognize their potential in drug interactions, and come up with plausible explanations for possible treatment resistance. This review will offer an overview of the varying concepts of tumor angiogenesis, several important angiogenic factors; focus on the role of anti-angiogenesis strategies in cancer treatment.
Topics: Humans; Immunotherapy; Neoplasms; Neovascularization, Pathologic
PubMed: 34147821
DOI: 10.1016/j.ctarc.2021.100422 -
Cell Death & Disease Jun 2023Microglia were considered as immune cells in inflammation until their angiogenic role was widely understood. Although the pro-inflammatory role of microglia in retinal...
Microglia were considered as immune cells in inflammation until their angiogenic role was widely understood. Although the pro-inflammatory role of microglia in retinal angiogenesis has been explored, little is known about its role in pro-angiogenesis and the microglia-endothelia interaction. Here, we report that galectin-3 (Gal3) released by activated microglia functions as a communicator between microglia and endothelia and competitively binds to Jag1, thus inhibiting the Notch signaling pathway and enhancing endothelial angiogenic metabolism to promote angiogenesis. These results suggest that Gal3 may be a novel and effective target in the treatment of retinal angiogenesis.
Topics: Galectin 3; Inflammation; Microglia; Neovascularization, Pathologic; Signal Transduction
PubMed: 37369647
DOI: 10.1038/s41419-023-05897-8 -
Molecular Oncology Mar 2018The C-type lectin-like domain of CLEC14a (CLEC14a-C-type lectin-like domain [CTLD]) is a key domain that mediates endothelial cell-cell contacts in angiogenesis....
The C-type lectin-like domain of CLEC14a (CLEC14a-C-type lectin-like domain [CTLD]) is a key domain that mediates endothelial cell-cell contacts in angiogenesis. However, the role of CLEC14a-CTLD in pathological angiogenesis has not yet been clearly elucidated. In this study, through complementarity-determining region grafting, consecutive deglycosylation, and functional isolation, we generated a novel anti-angiogenic human monoclonal antibody that specifically targets CLEC14a-CTLD and that shows improved stability and homogeneity relative to the parental antibody. We found that this antibody directly inhibits CLEC14a-CTLD-mediated endothelial cell-cell contact and simultaneously downregulates expression of CLEC14a on the surface of endothelial cells. Using various in vitro and in vivo functional assays, we demonstrated that this antibody effectively suppresses vascular endothelial growth factor (VEGF)-dependent angiogenesis and tumor angiogenesis of SNU182 human hepatocellular carcinoma, CFPAC-1 human pancreatic cancer, and U87 human glioma cells. Furthermore, we also found that this antibody significantly inhibits tumor angiogenesis of HCT116 and bevacizumab-adapted HCT116 human colorectal cancer cells. These findings suggest that antibody targeting of CLEC14a-CTLD has the potential to suppress VEGF-dependent angiogenesis and tumor angiogenesis and that CLEC14a-CTLD may be a novel anti-angiogenic target for VEGF-dependent angiogenesis and tumor angiogenesis.
Topics: Animals; Antibodies, Monoclonal; Cell Adhesion Molecules; Cell Communication; Cell Line, Tumor; Female; HCT116 Cells; Human Umbilical Vein Endothelial Cells; Humans; Immunoglobulin G; Lectins, C-Type; Mice; Mice, Inbred BALB C; Mice, Nude; Neovascularization, Pathologic; Neovascularization, Physiologic; Vascular Endothelial Growth Factor A; Xenograft Model Antitumor Assays
PubMed: 29316206
DOI: 10.1002/1878-0261.12169 -
Trends in Endocrinology and Metabolism:... Aug 2020Angiogenesis is crucial for the development of the blood vasculature during embryogenesis, but also contributes to cancer and other diseases. While therapeutic targeting... (Review)
Review
Angiogenesis is crucial for the development of the blood vasculature during embryogenesis, but also contributes to cancer and other diseases. While therapeutic targeting of endothelial cells (ECs) through growth factor inhibition is limited by insufficient efficacy and resistance, a new paradigm for modulating angiogenesis by targeting EC metabolism has emerged. Findings from the past decade highlight how ECs adapt their metabolism to proliferate or migrate during vessel sprouting, or to maintain the vascular barrier and protect themselves against oxidative stress in the high-oxygen environment they are exposed to in healthy conditions. We overview key endothelial metabolic pathways underlying the different EC phenotypes, as well as potential opportunities for targeting EC metabolism in therapeutic settings.
Topics: Animals; Endothelial Cells; Humans; Neovascularization, Pathologic; Neovascularization, Physiologic; Oxidative Stress
PubMed: 32622584
DOI: 10.1016/j.tem.2020.05.009 -
International Angiology : a Journal of... Dec 2018Competitive inhibition of endothelial nitric oxide synthase (eNOS) is the main biological effect of asymmetric dimethylarginine (ADMA), i.e. the methylated derivative of... (Review)
Review
Competitive inhibition of endothelial nitric oxide synthase (eNOS) is the main biological effect of asymmetric dimethylarginine (ADMA), i.e. the methylated derivative of L-arginine. The resulting low level of NO is becoming one of the elements of pathogenesis of numerous cardiovascular disorders, mainly related to atherosclerosis, but also other metabolic diseases including type 2 diabetes. It appears that a high level of ADMA is not only a marker of pathological conditions such as chronic kidney failure, but also a significant factor which damages the endothelium. Despite multiple studies, the mechanisms of reducing the level of ADMA, which would allow to inhibit the progression of cardiovascular diseases and effective treatment, e.g. by means of L-arginine supplementation or medicines which are lowering ADMA levels, are still unclear. Perhaps, linking ADMA with the processes of new blood cell formation (angiogenesis) will allow us to explain these multifactor mechanisms.
Topics: Animals; Arginine; Atherosclerosis; Cardiovascular Diseases; Endothelial Cells; Humans; Neovascularization, Pathologic; Neovascularization, Physiologic; Plaque, Atherosclerotic; Signal Transduction; Up-Regulation
PubMed: 30256050
DOI: 10.23736/S0392-9590.18.04017-8