Abstract
The neo-angiogenesis process is crucial for solid tumor growth and invasion, as the vasculature provides metabolic support and access to the circulation. Tumor blood vessels differ from normal vessels by altered morphology, blood flow and permeability, and the “switch” of endothelial cells to an angiogenic phenotype is considered a hallmark of the malignant process. Recent evidence indicates that tumor-derived endothelial cells (TEC) possess a distinct and unique phenotype differing from normal endothelial cells at the molecular and functional levels. The anti-angiogenic therapies developed to date are based on tumor endothelial cells being genetically normal. However, it has recently been shown that TEC derived from different tumors are genetically unstable and may acquire resistance to drugs. It has been suggested that TEC may acquire cytogenetic abnormalities within the tumor microenvironment. We found that TEC from different tumors share characteristics in terms of pro-angiogenic properties, survival and resistance to chemotherapy in respect to non-tumor endothelial cells and maintain in vitro an immature pro-angiogenic phenotype in the absence of tumor cells. This was associated with an up-regulation of the AKT/PI3K pathway, involved in the repression of the anti-angiogenic factors thrombospondin-1 and PTEN, and the presence in TEC of the embryonic transcription factor PAX2, responsible for the expression of immature endothelial markers such as NCAM. The in vivo inhibitions of these pathways were shown to display an anti-angiogenic effect on TEC. This review considers the current studies on TEC abnormalities and discusses the hypothesis that at least part of tumor vessels may derive from an intra tumor ongoing embryonic-like vasculogenesis or from tissue endothelial cells switched to angiogenesis from genetic information transmitted from the tumor.
Keywords: Tumor endothelial cells, angiogenesis, vasculogenesis, origin of tumor endothelial cells, stem cells
Current Vascular Pharmacology
Title: Characterization of Molecular and Functional Alterations of Tumor Endothelial Cells to Design Anti-Angiogenic Strategies
Volume: 8 Issue: 2
Author(s): Benedetta Bussolati, Maria Chiara Deregibus and Giovanni Camussi
Affiliation:
Keywords: Tumor endothelial cells, angiogenesis, vasculogenesis, origin of tumor endothelial cells, stem cells
Abstract: The neo-angiogenesis process is crucial for solid tumor growth and invasion, as the vasculature provides metabolic support and access to the circulation. Tumor blood vessels differ from normal vessels by altered morphology, blood flow and permeability, and the “switch” of endothelial cells to an angiogenic phenotype is considered a hallmark of the malignant process. Recent evidence indicates that tumor-derived endothelial cells (TEC) possess a distinct and unique phenotype differing from normal endothelial cells at the molecular and functional levels. The anti-angiogenic therapies developed to date are based on tumor endothelial cells being genetically normal. However, it has recently been shown that TEC derived from different tumors are genetically unstable and may acquire resistance to drugs. It has been suggested that TEC may acquire cytogenetic abnormalities within the tumor microenvironment. We found that TEC from different tumors share characteristics in terms of pro-angiogenic properties, survival and resistance to chemotherapy in respect to non-tumor endothelial cells and maintain in vitro an immature pro-angiogenic phenotype in the absence of tumor cells. This was associated with an up-regulation of the AKT/PI3K pathway, involved in the repression of the anti-angiogenic factors thrombospondin-1 and PTEN, and the presence in TEC of the embryonic transcription factor PAX2, responsible for the expression of immature endothelial markers such as NCAM. The in vivo inhibitions of these pathways were shown to display an anti-angiogenic effect on TEC. This review considers the current studies on TEC abnormalities and discusses the hypothesis that at least part of tumor vessels may derive from an intra tumor ongoing embryonic-like vasculogenesis or from tissue endothelial cells switched to angiogenesis from genetic information transmitted from the tumor.
Export Options
About this article
Cite this article as:
Bussolati Benedetta, Deregibus Chiara Maria and Camussi Giovanni, Characterization of Molecular and Functional Alterations of Tumor Endothelial Cells to Design Anti-Angiogenic Strategies, Current Vascular Pharmacology 2010; 8 (2) . https://dx.doi.org/10.2174/157016110790887036
DOI https://dx.doi.org/10.2174/157016110790887036 |
Print ISSN 1570-1611 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6212 |
Call for Papers in Thematic Issues
Advancements in Arterial Stiffness: Novel Therapeutic Frontiers
Arterial stiffness, a hallmark of cardiovascular disease, poses significant challenges in contemporary healthcare. This thematic issue delves into the multifaceted landscape of arterial stiffness and explores cutting-edge therapeutic interventions aimed at mitigating its adverse effects. Within these pages, readers will find a comprehensive overview of the mechanisms underlying arterial stiffness, ...read more
Ischemic Cardiovascular Diseases: Mechanisms, Diagnosis and Therapy
Ischemic cardiovascular disease includes myocardial infarction, coronary atherosclerotic heart disease, angina pectoris, etc., constitute the leading cause of patient mortality by preventing tissues from getting sufficient oxygen and nutrients. Ischemic heart disease, as a clinical condition, is characterized by myocardial ischemia, causing an imbalance between myocardial blood supply and demand, ...read more
TREATMENT OF CARDIOVASCULAR DISEASE IN CHRONIC AND END STAGE KIDNEY DISEASE
Cardiovascular disease still remains the leading cause of death in Chronic and End Stage Kidney Disease, accounting for more than half of all deaths in dialysis patients. During the past decade, research has been focused on novel therapeutic agents that might delay or even reverse cardiovascular disease and vascular calcification, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Mitochondrial Drug Targets in Cell Death and Cancer
Current Pharmaceutical Design Ornithine Decarboxylase Inhibition: A Strategy to Combat Various Diseases
Mini-Reviews in Medicinal Chemistry Recent Advances in Antabuse (Disulfiram): The Importance of its Metal-binding Ability to its Anticancer Activity
Current Medicinal Chemistry Evolution of the Strategies for Screening and Identifying Human Tumor Antigens
Current Protein & Peptide Science Alteration of Isocitrate Dehydrogenase Following Acute Ischemic Injury as a Means to Improve Cellular Energetic Status in Neuroadaptation
CNS & Neurological Disorders - Drug Targets RECKing MMP: Relevance of Reversion-inducing Cysteine-rich Protein with Kazal Motifs as a Prognostic Marker and Therapeutic Target for Cancer (A Review)
Anti-Cancer Agents in Medicinal Chemistry Recurrent Scalp Lesions from Glioblastoma: Case Report and Literature Review
Current Cancer Therapy Reviews Targeted Toxins for Glioblastoma Multiforme: Pre-Clinical Studies and Clinical Implementation
Anti-Cancer Agents in Medicinal Chemistry The Role of Shcbp1 in Signaling and Disease
Current Cancer Drug Targets Search and Rescue: Identification of Cannabinoid Actions Relevant for Neuronal Survival and Protection
Current Neuropharmacology Peptide modules for overcoming barriers of nucleic acids transport to cells
Current Topics in Medicinal Chemistry Pharmacogenetics of Non-small Cell Lung Cancer (NSCLC): Time to "Work it Out"?
Current Pharmaceutical Design Recent Evidence of the Regulatory Role of PPARs in Neural Stem Cells and Their Underlying Mechanisms for Neuroprotective Effects
Current Stem Cell Research & Therapy Dysregulated Pathway Identification of Alzheimer's Disease Based on Internal Correlation Analysis of Genes and Pathways
Combinatorial Chemistry & High Throughput Screening Cell Penetrating Peptides for Tumor Targeting
Current Pharmaceutical Biotechnology Therapeutic Implications of Superoxide Dismutase And Its Importance in Kinase Drug Discovery
Current Topics in Medicinal Chemistry Ketogenic Diet Acts on Body Remodeling and MicroRNAs Expression Profile
MicroRNA Benzofuran Small Molecules as Potential Inhibitors of Human Protein Kinases. A Review
Current Pharmaceutical Design Aflibercept: A Novel VEGF Targeted Agent to Explore the Future Perspectives of Anti-Angiogenic Therapy for the Treatment of Multiple Tumors
Mini-Reviews in Medicinal Chemistry Recent Study of Dual HDAC/PARP Inhibitor for the Treatment of Tumor
Current Topics in Medicinal Chemistry