scholarly journals Characteristics of tumor-associated endothelial cells derived from glioblastoma multiforme

2006 ◽  
Vol 20 (4) ◽  
pp. E22 ◽  
Author(s):  
Christiana Charalambous ◽  
Thomas C. Chen ◽  
Florence M. Hofman
Keyword(s):  
Endothelial Cells ◽  
Antiangiogenic Therapy ◽  
Cell Types ◽  
Antiangiogenic Agents ◽  
Normal Brain ◽  
Vascular Endothelial ◽  
Phenotypic Characteristics ◽  
Normal Human ◽  
Endothelial Growth Factor

✓ Glioblastomas multiforme (GBMs) are highly vascular brain tumors characterized by abnormal vessel structures in vivo. This finding supports the theory that glioma-associated endothelial cells (ECs) have intrinsically different properties from ECs in normal human brain. Therefore, identification of the functional and phenotypic characteristics of tumor-associated ECs is essential for designing a rational antiangiogenic therapy. The GBM-associated ECs have a large, flat, and veil-like appearance, in contrast to normal ones, which are small and plump. Although the tumor ECs have the typical markers, they proliferate more slowly than these cell types in normal brain. The GBM-associated ECs are resistant to cytotoxic drugs, and they undergo less apoptosis than control cells. Also, GBM-associated ECs migrate faster than controls and constitutively produce high levels of growth factors such as endothelin-1, interleukin-8, and vascular endothelial growth factor. An understanding of these unique characteristics of glioma-associated ECs is important for the development of novel antiangiogenic agents that specifically target tumor-associated ECs in gliomas.

Interaction between vascular endothelial cells and vascular intimal spindle-shaped cells in vitro

1983 ◽  
Vol 60 (1) ◽  
pp. 89-102
Author(s):  
D de Bono ◽  
C. Green
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Three Dimensional ◽  
Vascular Endothelial ◽  
Pure Cultures ◽  
Species Specific ◽  
Endothelial Growth Factor

The interactions between human or bovine vascular endothelial cells and fibroblast-like vascular intimal spindle-shaped cells have been studied in vitro, using species-specific antibodies to identify the different components in mixed cultures. Pure cultures of endothelial cells grow as uniform, nonoverlapping monolayers, but this growth pattern is lost after the addition of spindle cells, probably because the extracellular matrix secreted by the latter causes the endothelial cells to modify the way they are attached to the substrate. The result is a network of tubular aggregates of endothelial cells in a three-dimensional ‘polylayer’ of spindle-shaped cells. On the other hand, endothelial cells added to growth-inhibited cultures of spindle-shaped cells will grow in sheets over the surface of the culture. Human endothelial cells grown in contact with spindle-shaped cells have a reduced requirement for a brain-derived endothelial growth factor. The interactions of endothelial cells and other connective tissue cells in vitro may be relevant to the mechanisms of endothelial growth and blood vessel formation in vivo, and emphasize the potential importance of extracellular matrix in controlling endothelial cell behaviour.

Vascular endothelial growth factor–stimulated endothelial cells promote adhesion and activation of platelets

Blood ◽  
2000 ◽  
Vol 96 (13) ◽  
pp. 4216-4221 ◽  
Author(s):  
Henk M. W. Verheul ◽  
Anita S. Jorna ◽  
Klaas Hoekman ◽  
Henk J. Broxterman ◽  
Martijn F. B. G. Gebbink ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Platelet Adhesion ◽  
Umbilical Vein ◽  
Vascular Endothelial ◽  
High Affinity Binding Site ◽  
Umbilical Vein Endothelial Cells ◽  
Endothelial Growth Factor

Abstract Coagulation abnormalities, including an increased platelet turnover, are frequently found in patients with cancer. Because platelets secrete angiogenic factors on activation, this study tested the hypothesis that platelets contribute to angiogenesis. Stimulation with vascular endothelial growth factor (VEGF, 25 ng/mL) of human umbilical vein endothelial cells (HUVECs) promoted adhesion of nonactivated platelets 2.5-fold. In contrast, stimulation of HUVECs with basic fibroblast growth factor (bFGF) did not promote platelet adhesion. By blocking tissue factor (TF) activity, platelet adhesion was prevented and antibodies against fibrin(ogen) and the platelet-specific integrin, αIIbβ3, inhibited platelet adhesion for 70% to 90%. These results indicate that VEGF-induced platelet adhesion to endothelial cells is dependent on activation of TF. The involvement of fibrin(ogen) and the αIIbβ3 integrin, which exposes a high-affinity binding site for fibrin(ogen) on platelet activation, indicates that these adhering platelets are activated. This was supported by the finding that the activity of thrombin, a product of TF-activated coagulation and a potent platelet activator, was required for platelet adhesion. Finally, platelets at physiologic concentrations stimulated proliferation of HUVECs, indicative of proangiogenic activity in vivo. These results support the hypothesis that platelets contribute to tumor-induced angiogenesis. In addition, they may explain the clinical observation of an increased platelet turnover in cancer patients. Platelets may also play an important role in other angiogenesis-dependent diseases in which VEGF is involved, such as diabetes and autoimmune diseases.

Origin and diversity of embryonic endothelium/endocardium

2018 ◽  
Author(s):  
LeShana SaintJean ◽  
H.S. Baldwin
Keyword(s):  
Endothelial Cells ◽  
Heart Development ◽  
Vascular Endothelial Cells ◽  
Coronary Vessels ◽  
Cell Types ◽  
Genetic Profile ◽  
Vascular Endothelial ◽  
Tremendous Progress

The endocardium represents a distinct population of endothelial cells that arises during the initiation of heart development. Endocardial cells can easily be distinguished from most of the other cardiac cell types. However, endocardial and vascular endothelial cells contain a similar genetic profile that limits the ability to study each group independently. Despite these limitations, tremendous progress has been made in identifying the different roles of endocardial cells throughout heart development. Initial studies focused on the origin of endocardial cells and their role in valvulogenesis, trabeculation, and formation of the ventricular and atrial septum. With the advancement of microscopy and the availability of endocardial specific reporter models (in vitro and in vivo) we have obtained more insight into the molecular, structural, and functional complexity of the endocardium. Additional studies have demonstrated how the endocardium is also involved in the development of coronary vessels within the compact myocardium and in heart regeneration.

ABERRANT ANGIOGENIC CHARACTERISTICS OF HUMAN BRAIN ARTERIOVENOUS MALFORMATION ENDOTHELIAL CELLS

Neurosurgery ◽  
2009 ◽  
Vol 64 (1) ◽  
pp. 139-148 ◽  
Author(s):  
Mark N. Jabbour ◽  
James B. Elder ◽  
Christian G. Samuelson ◽  
Shabnam Khashabi ◽  
Florence M. Hofman ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Growth Factor Receptors ◽  
Boyden Chamber ◽  
Normal Brain ◽  
Vascular Endothelial ◽  
Brain Endothelial Cells ◽  
Control Brain ◽  
Endothelial Growth Factor

Abstract OBJECTIVE To identify and characterize the phenotypic and functional differences of endothelial cells derived from cerebral arteriovenous malformations (AVM), as compared with endothelial cells derived from a normal brain. METHODS Isolated AVM brain endothelial cells and control brain endothelial cells were evaluated immunohistochemically for expression of the endothelial cell markers von Willebrand factor and CD31, as well as angiogenic factors including vascular endothelial growth factor A, interleukin-8, and endothelin-1. Vascular endothelial growth factor receptors 1 and 2 were also evaluated using immunohistochemistry techniques. Functional assays evaluated cell proliferation, cytokine production, tubule formation, and cell migration using the modified Boyden chamber technique. RESULTS Endothelial cells derived from AVMs expressed high levels of vascular endothelial growth factor A and significantly overexpressed the vascular endothelial growth factor receptors 1 and 2 (P < 0.05), as compared with control endothelial cells. In addition, comparison to control brain endothelial cells demonstrated that AVM brain endothelial cells proliferated faster, migrated more quickly, and produced aberrant tubule-like structures. CONCLUSION Endothelial cells derived from cerebral AVMs are highly activated cells overexpressing proangiogenic growth factors and exhibiting abnormal functions consistent with highly activated endothelial cells.

The angiopoietin 1/angiopoietin 2 balance as a prognostic marker in primary glioblastoma multiforme

2009 ◽  
Vol 110 (1) ◽  
pp. 147-155 ◽  
Author(s):  
Mariska Sie ◽  
Michiel Wagemakers ◽  
Grietje Molema ◽  
Jan Jakob A. Mooij ◽  
Eveline S. J. M. de Bont ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Antiangiogenic Therapy ◽  
Special Focus ◽  
Vascular Endothelial ◽  
Ki 67 ◽  
Primary Glioblastoma ◽  
Polymerase Chain ◽  
Angiopoietin 2 ◽  
Endothelial Growth Factor ◽  
Tumor Area

Object In the present study, the authors analyzed the ANGPT1/ANGPT2 balance in the context of therapeutic outcome in 62 patients with primary glioblastomas multiforme (GBMs). Methods The tumor tissue used was obtained in adult patients who underwent neurosurgical debulking. Microvessel density was assessed by morphometric analysis. Double immunostaining for Ki 67/CD34 and cleaved caspase-3/CD34 was used to investigate the proliferation and apoptotic fraction of both endothelial and tumor cells. The expression of VEGFs (A–D) was evaluated on immunohistochemistry. To measure tumor vascular stabilization, the ANGPT1/ANGPT2 mRNA balance was determined using real-time reverse transcriptase polymerase chain reaction. Results Within the hypoxic perinecrotic tumor area, the apoptotic fraction of endothelial cells was positively correlated with VEGFA expression (p < 0.001). Higher levels of VEGFA correlated with greater proliferation of endothelial cells in the intermediate tumor area (p = 0.031). Vascular endothelial growth factor D was significantly more highly expressed within the perinecrotic tumor area compared with the intermediate tumor area (p < 0.001). Multivariate analysis showed a significant association between the ANGPT1/ANGPT2 balance and the survival time of patients with GBMs (p = 0.035). Conclusions The results of the present study suggest that the ANGPT1/ANGPT2 balance has prognostic value in patients with primary GBMs. The authors' findings support the need for further studies of the feasibility of antiangiogenic therapy in primary GBMs, with a special focus on the normalization of tumor vasculature.

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