-
BMB Reports Jun 2020Tumor angiogenesis is an essential process for growth and metastasis of cancer cells as it supplies tumors with oxygen and nutrients. During tumor angiogenesis, many... (Review)
Review
Tumor angiogenesis is an essential process for growth and metastasis of cancer cells as it supplies tumors with oxygen and nutrients. During tumor angiogenesis, many pro-angiogenic factors are secreted by tumor cells to induce their own vascularization via activation of pre-existing host endothelium. However, accumulating evidence suggests that vasculogenic mimicry (VM) is a key alternative mechanism for tumor vascularization when tumors are faced with insufficient supply of oxygen and nutrients. VM is a tumor vascularization mechanism in which tumors create a blood supply system, in contrast to tumor angiogenesis mechanisms that depend on pre-existing host endothelium. VM is closely associated with tumor progression and poor prognosis in many cancers. Therefore, inhibition of VM may be a promising therapeutic strategy and may overcome the limitations of anti-angiogenesis therapy for cancer patients. In this review, we provide an overview of the current anti-angiogenic therapies for ovarian cancer and the current state of knowledge regarding the links between microRNAs and the VM process, with a focus on the mechanism that regulates associated signaling pathways in ovarian cancer. Moreover, we discuss the potential for VM as a therapeutic strategy against ovarian cancer. [BMB Reports 2020; 53(6): 291-298].
Topics: Antineoplastic Agents; Female; Humans; MicroRNAs; Neovascularization, Pathologic; Ovarian Neoplasms; Signal Transduction
PubMed: 32438972
DOI: 10.5483/BMBRep.2020.53.6.060 -
Frontiers in Oncology 2021Breast cancer is the most common cancer affecting women and is the second leading cause of cancer related death worldwide. Angiogenesis, the process of new blood vessel... (Review)
Review
Breast cancer is the most common cancer affecting women and is the second leading cause of cancer related death worldwide. Angiogenesis, the process of new blood vessel development from pre-existing vasculature, has been implicated in the growth, progression, and metastasis of cancer. Tumor angiogenesis has been explored as a key therapeutic target for decades, as the blockade of this process holds the potential to reduce the oxygen and nutrient supplies that are required for tumor growth. However, many existing anti-angiogenic approaches, such as those targeting Vascular Endothelial Growth Factor, Notch, and Angiopoietin signaling, have been associated with severe side-effects, limited survival advantage, and enhanced cancer regrowth rates. To address these setbacks, alternative pathways involved in the regulation of tumor angiogenesis are being explored, including those involving Bone Morphogenetic Protein-9 signaling, the Sonic Hedgehog pathway, Cyclooxygenase-2, p38-mitogen-activated protein kinase, and Chemokine Ligand 18. This review article will introduce the concept of tumor angiogenesis in the context of breast cancer, followed by an overview of current anti-angiogenic therapies, associated resistance mechanisms and novel therapeutic targets.
PubMed: 34926282
DOI: 10.3389/fonc.2021.772305 -
Cancer Microenvironment : Official... Jun 2018The development of cancer involves an intricate process, wherein many identified and unidentified factors play a role. Tumor angiogenesis, growth of new blood vessels,... (Review)
Review
The development of cancer involves an intricate process, wherein many identified and unidentified factors play a role. Tumor angiogenesis, growth of new blood vessels, is one of the major prerequisites for tumor growth as tumor cells rely on adequate oxygen and nutrient supply as well as the removal of waste products. Growth factors including VEGF orchestrate the development of angiogenesis. In addition, nervous system via the release of neurotransmitters contributes to tumor angiogenesis. The nervous system governs functional activities of many organs, and, as tumors are not independent organs within an organism, this system is integrally involved in tumor growth and progression via regulating tumor angiogenesis. Various neurotransmitters have been reported to play an important role in tumor angiogenesis.
PubMed: 29502307
DOI: 10.1007/s12307-018-0207-3 -
Molecular Therapy Oncolytics Sep 2021Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) execute a wide array of functions in physiological and pathological processes, including tumor progression.... (Review)
Review
Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) execute a wide array of functions in physiological and pathological processes, including tumor progression. Angiogenesis, an elaborate multistep process driving new blood vessel formation, accelerates cancer progression by supplying nutrients and energy. Dysregulated lncRNAs and circRNAs can reportedly impact cancer progression by influencing angiogenesis. However, the expanding landscape of lncRNAs and circRNAs in tumor progression-dependent angiogenesis remains largely unknown. This review summarizes the major functions of angiogenic lncRNAs (Angio-LncRs) and angiogenic circRNAs (termed Angio-CircRs) and their cancer mechanisms. Moreover, we highlight the commonalities of lncRNAs and circRNAs in epigenetic, transcriptional, and post-transcriptional regulation as well as illustrate how Angio-LncRs and Angio-CircRs induce cancer onset and progression. We also discuss their potential clinical applications in diagnosis, prognosis, and anti-angiogenic therapies.
PubMed: 34553023
DOI: 10.1016/j.omto.2021.07.001 -
Histology and Histopathology Feb 2012The Notch signaling pathway is critical for many developmental processes including physiologic angiogenesis. Notch is also implicated in having a key role in tumor... (Review)
Review
The Notch signaling pathway is critical for many developmental processes including physiologic angiogenesis. Notch is also implicated in having a key role in tumor angiogenesis. Preclinical and clinical experience with anti-angiogenic strategies indicates that they may be limited by tumor resistance and recurrence, which has led to the search for alternative angiogenic treatment strategies. Significant progress has been made in shedding light on the complex mechanisms by which Notch signaling can influence tumor growth by disrupting vasculature in an array of tumor models (Ridgway et al., 2006). These results have led to the consideration of Notch as an attractive target to block tumor angiogenesis and inhibit growth. However, studies of inhibition of Notch signaling in different tumor models have uncovered similarly variable results, and some unexpected adverse effects. The ability of Notch to function in a context-dependent manner as a determinant of cell fate, a tumor suppressor, and an oncogene may partially explain the complexity in interpreted the role of Notch signaling inhibitors in preclinical tumor studies. In addition, Notch may also play an important role in metastasis via its direct effects on the vasculature and by modulation of epithelial-mesenchymal transition in tumor cells. Here we present a current understanding of Notch signaling in tumor angiogenesis, and discuss recent work on the role of Notch in tumor metastatic progression.
Topics: Animals; Humans; Neoplasm Metastasis; Neoplasms; Neovascularization, Pathologic; Receptors, Notch; Signal Transduction
PubMed: 22207549
DOI: 10.14670/HH-27.151 -
Biochimica Et Biophysica Acta. Reviews... Apr 2020Redox reactions pervade all biology. The control of cellular redox state is essential for bioenergetics and for the proper functioning of many biological functions. This... (Review)
Review
Redox reactions pervade all biology. The control of cellular redox state is essential for bioenergetics and for the proper functioning of many biological functions. This review traces a timeline of findings regarding the connections between redox and cancer. There is ample evidence of the involvement of cellular redox state on the different hallmarks of cancer. Evidence of the control of tumor angiogenesis and metastasis through modulation of cell redox state is reviewed and highlighted.
Topics: Disease Progression; Humans; Neoplasms; Neovascularization, Pathologic; Oxidation-Reduction; Signal Transduction
PubMed: 32035101
DOI: 10.1016/j.bbcan.2020.188352 -
Biomolecules Jan 2020Several phytochemicals have been identified for their role in modifying miRNA regulating tumor progression. miRNAs modulate the expression of several oncogenes and tumor... (Review)
Review
Several phytochemicals have been identified for their role in modifying miRNA regulating tumor progression. miRNAs modulate the expression of several oncogenes and tumor suppressor genes including the genes that regulate tumor angiogenesis. Hypoxia inducible factor-1 alpha (HIF-1α) signaling is a central axis that activates oncogenic signaling and acts as a metabolic switch in endothelial cell (EC) driven tumor angiogenesis. Tumor angiogenesis driven by metabolic reprogramming of EC is crucial for tumor progression and metastasis in many different cancers, including breast cancers, and has been linked to aberrant miRNA expression profiles. In the current article, we identify different miRNAs that regulate tumor angiogenesis in the context of oncogenic signaling and metabolic reprogramming in ECs and review how selected phytochemicals could modulate miRNA levels to induce an anti-angiogenic action in breast cancer. Studies involving genistein, epigallocatechin gallate (EGCG) and resveratrol demonstrate the regulation of miRNA-21, miRNA-221/222 and miRNA-27, which are prognostic markers in triple negative breast cancers (TNBCs). Modulating the metabolic pathway is a novel strategy for controlling tumor angiogenesis and tumor growth. Cardamonin, curcumin and resveratrol exhibit their anti-angiogenic property by targeting the miRNAs that regulate EC metabolism. Here we suggest that using phytochemicals to target miRNAs, which in turn suppresses tumor angiogenesis, should have the potential to inhibit tumor growth, progression, invasion and metastasis and may be developed into an effective therapeutic strategy for the treatment of many different cancers where tumor angiogenesis plays a significant role in tumor growth and progression.
Topics: Angiogenesis Inhibitors; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Chalcones; Curcumin; Disease Progression; Endothelial Cells; Female; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; MicroRNAs; Neoplasm Invasiveness; Neoplasm Metastasis; Neovascularization, Pathologic; Oxygen; Phytochemicals; Phytotherapy; Prognosis; Reactive Oxygen Species; Resveratrol; Signal Transduction
PubMed: 32012744
DOI: 10.3390/biom10020191 -
Journal of Oncology 2010
PubMed: 20886025
DOI: 10.1155/2010/761671 -
The International Journal of... 2022The development and homeostasis of vertebrate organisms depend on the "tree of life", in other words, the intricate network of vascular tubes composed of endothelial... (Review)
Review
The development and homeostasis of vertebrate organisms depend on the "tree of life", in other words, the intricate network of vascular tubes composed of endothelial cells attached to the basement membrane and surrounded by perivascular cells. Although many studies have revealed the fundamental role of cytokines, growth factors and Notch signalling in vascular morphogenesis, we still lack sufficient understanding of the molecular mechanisms controlling the various steps of the angiogenic processes. Emerging data highlight that cell adhesions are key players in vascular morphogenesis. In this review, we focus on endothelial cells and we present the current state of knowledge regarding the role of cell-matrix adhesions in developmental and tumour angiogenesis, attained mainly from genetic studies and animal models.
Topics: Animals; Cell-Matrix Junctions; Endothelial Cells; Morphogenesis; Neoplasms; Neovascularization, Physiologic
PubMed: 34881799
DOI: 10.1387/ijdb.210204vk -
Cancer Research Communications Dec 2022Neuropilin (NRP) expression is highly correlated with poor outcome in multiple cancer subtypes. As known coreceptors for VEGFRs, core drivers of angiogenesis, past...
UNLABELLED
Neuropilin (NRP) expression is highly correlated with poor outcome in multiple cancer subtypes. As known coreceptors for VEGFRs, core drivers of angiogenesis, past investigations have alluded to their functional roles in facilitating tumorigenesis by promoting invasive vessel growth. Despite this, it remains unclear as to whether NRP1 and NRP2 act in a synergistic manner to enhance pathologic angiogenesis. Here we demonstrate, using NRP1 , NRP2 , and NRP1/NRP2 mouse models, that maximum inhibition of primary tumor development and angiogenesis is achieved when both endothelial NRP1 and NRP2 are targeted simultaneously. Metastasis and secondary site angiogenesis were also significantly inhibited in NRP1/NRP2 animals. Mechanistic studies revealed that codepleting NRP1 and NRP2 in mouse-microvascular endothelial cells stimulates rapid shuttling of VEGFR-2 to Rab7 endosomes for proteosomal degradation. Our results highlight the importance of targeting both NRP1 and NRP2 to modulate tumor angiogenesis.
SIGNIFICANCE
The findings presented in this study demonstrate that tumor angiogenesis and growth can be arrested completely by cotargeting endothelial NRP1 and NRP2. We provide new insight into the mechanisms of action regulating NRP-dependent tumor angiogenesis and signpost a novel approach to halt tumor progression.
Topics: Animals; Mice; Neuropilin-1; Neuropilin-2; Endothelial Cells; Neovascularization, Pathologic; Neoplasms
PubMed: 36970722
DOI: 10.1158/2767-9764.CRC-22-0250