Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TEL/ETV6 is the frequent target of translocations associated with lymphoid and myeloid leukemias and solid tumors. We show that TEL induces aggregation of immortalized and transformed fibroblasts, endothelial cells and astrocytes. These aggregates form cellular cords in NIH3T3-UCLA by a cell autonomous process, which occurs when the monolayer is made up of over 75% of cells expressing exogenous TEL. Cords with a diameter of 15-25 microm contain a lumen and occur as tube structures. The possible relevance for vasculogenic mimicry is discussed. By contrast TEL did not induce aggregation of regular NIH3T3 cells, an effect that could only be induced by co-expression of oncogenic RAS/Lys12. Also transduction of TEL and RAS retroviral vectors into the endothelial MS1 cell line and TEL alone in the highly transformed glioblastoma cell lines EH-A and EH-B resulted in extensive aggregation. Thus, the induction of cellular aggregation by TEL correlates with transformation.
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PMID:TEL Induces Aggregation in Transformed Cells and Induces Tube Formation in NIH3T3-UCLA Cells. 1186 39

Vasculogenic mimicry (VM) has been observed in melanoma and in some nonmelanoma tumor types. It is unknown whether a similar VM phenomenon exists in astrocytoma. The present study was to examine 45 astrocytomas (including World Health Organization grade II 15 cases, grade III 15 cases, and grade IV 15 cases) by CD34 endothelial marker periodic acid-Schiff (PAS) dual staining to see if VM existing in these tumors. The results demonstrated that endothelium-lined vessels dominated the tumor microvasculature and stained positively for PAS, laminin, and endothelial marker. PAS-positive pattern of VM was found in two grade IV astrocytomas. Channels stained positively for PAS, laminin, and negatively for CD34 of the VM entrapped in the tumor tissue. Erythrocytes could be observed in some of these channels. In these networks of PAS-positive pattern, spots of weak reaction for CD34 were observed, suggesting the incorporation of VM channel and normal vessel. Furthermore, in astrocytoma, especially glioblastoma, focus of anaplastic tumor cells appeared with CD34 expression, whereas some tumor cells lost glial fibrillary acid protein expression. It is assumed that genetically deregulated tumor cells in astrocytoma could lose the astrocyte-specific protein and express inappropriate markers not expected in cells of astrocyte lineage. The present results suggest that VM phenomenon exists in some malignant astrocytoma.
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PMID:Does vasculogenic mimicry exist in astrocytoma? 1592 71

In 1999, Maniotis described a novel process by which tumors develop a highly patterned microcirculation that was independent of angiogenesis: in aggressive primary and metastatic melanomas, tumor cells generate non-endothelial cell-lined microcirculatory channels composed of extracellular matrix and lined externally by tumor cells. They named the process "vasculogenic mimicry" (VM). Folberg used PAS staining to show VM network, and identified 7 morphologic patterns of PAS-positive channels uveal melanomas which were confirmed as tubular type and patterned matrix type. Maniotis suggested PAS-positive patterns of VM in uveal melanoma are indeed a form of tumor microcirculation which is different from angiogenesis, and it is not a stromal host response at the interface between the tumor and the surrounding host stroma. VM has also been observed in carcinomas of the breast, prostate, ovary and lung, glioblastoma, synoviosarcoma, rhabdomyosarcoma, and phaeochromocytoma, and in the process of placenta formation from cytotrophoblasts. The molecular "signature" of aggressive melanoma cells is illustrative of an undifferentiated cell with a gene expression profile that is similar to that of embryonic-like cells. VE-cadherin, EphA2, laminin5 gamma2, matrix metalloproteinases (MMPs), vascular endothelial growth factor-C (VEGF-C), LYVE1, TF and NOTCH are important components of molecular switch of vasculogenic mimicry. The heterogeneity of tumor vasculature and the molecular regulation mechanisms present an opportunity for tumor therapy.
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PMID:[Vasculogenic mimicry--potential target for tumor therapy]. 1683 Dec 90

Glioblastoma is one of the most angiogenic human tumours and endothelial proliferation is a hallmark of the disease. A better understanding of glioblastoma vasculature is needed to optimize anti-angiogenic therapy that has shown a high but transient efficacy. We analysed human glioblastoma tissues and found non-endothelial cell-lined blood vessels that were formed by tumour cells (vasculogenic mimicry of the tubular type). We hypothesized that CD133+ glioblastoma cells presenting stem-cell properties may express pro-vascular molecules allowing them to form blood vessels de novo. We demonstrated in vitro that glioblastoma stem-like cells were capable of vasculogenesis and endothelium-associated genes expression. Moreover, a fraction of these glioblastoma stem-like cells could transdifferentiate into vascular smooth muscle-like cells. We describe here a new mechanism of alternative glioblastoma vascularization and open a new perspective for the antivascular treatment strategy.
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PMID:A new alternative mechanism in glioblastoma vascularization: tubular vasculogenic mimicry. 2035 1

Glioblastoma is a highly angiogenetic malignancy, the neoformed vessels of which are thought to arise by sprouting of pre-existing brain capillaries. The recent demonstration that a population of glioblastoma stem-like cells (GSCs) maintains glioblastomas indicates that the progeny of these cells may not be confined to the neural lineage. Normal neural stem cells are able to differentiate into functional endothelial cells. The connection between neural stem cells and the endothelial compartment seems to be critical in glioblastoma, where cancer stem cells closely interact with the vascular niche and promote angiogenesis through the release of vascular endothelial growth factor (VEGF) and stromal-derived factor 1 (refs 5-9). Here we show that a variable number (range 20-90%, mean 60.7%) of endothelial cells in glioblastoma carry the same genomic alteration as tumour cells, indicating that a significant portion of the vascular endothelium has a neoplastic origin. The vascular endothelium contained a subset of tumorigenic cells that produced highly vascularized anaplastic tumours with areas of vasculogenic mimicry in immunocompromised mice. In vitro culture of GSCs in endothelial conditions generated progeny with phenotypic and functional features of endothelial cells. Likewise, orthotopic or subcutaneous injection of GSCs in immunocompromised mice produced tumour xenografts, the vessels of which were primarily composed of human endothelial cells. Selective targeting of endothelial cells generated by GSCs in mouse xenografts resulted in tumour reduction and degeneration, indicating the functional relevance of the GSC-derived endothelial vessels. These findings describe a new mechanism for tumour vasculogenesis and may explain the presence of cancer-derived endothelial-like cells in several malignancies.
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PMID:Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells. 2121 67

Glioblastoma is one of the most angiogenic human tumors and characterized by microvascular proliferations. A better understanding of glioblastoma vasculature is needed to optimize anti-angiogenic therapy that has shown a promising but incomplete efficacy. The present study examined 48 glioblastomas by CD34 endothelial marker periodic acid-Schiff (PAS) dual staining and found non-endothelial cell-lined blood vessels that were formed by tumor cells (vasculogenic mimicry, VM) existing in a fraction of these tumors. We hypothesized that CD133-positive glioblastoma stem-like cells (GSCs) may play a pivotal role in glioblastoma VM formation and then demonstrated in vitro and in vivo that a subset of GSCs were capable of vasculogenesis. Moreover, we found that several growth factors involved in normal angiogenesis were expressed in GSCs. We describe here a new mechanism of alternative glioblastoma vascularization and open a new perspective for the anti-vascular treatment strategy.
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PMID:Vasculogenic mimicry-potential target for glioblastoma therapy: an in vitro and in vivo study. 2116 44

The blood-brain barrier (BBB) presents a significant obstacle to delivery of targeted therapies to brain tumors. In this issue of the JCI, Staquicini and colleagues apply an in vivo phage-displayed library of random peptides to identify differentially expressed peptides that can be used to transport targeted agents across the intact BBB. The authors uncover a non-canonical, peptide-mediated iron-mimicry mechanism to induce transport of the transferrin/transferrin receptor complex across the BBB. They then demonstrate the ability of phage-targeting approaches to deliver therapeutic cargo and molecular imaging reporters across the BBB in an intracranial glioblastoma mouse model.
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PMID:Charting the course across the blood-brain barrier. 2118 93

Glioblastoma is one of the most angiogenic malignancy, the neoplastic vessels of which are likely to arise by angiogenesis and vasculogenesis. An alternative mechanism of tumor vasculature is described, termed vasculogenic mimicry, by which highly aggressive tumor cells can form vessel-like structures themselves, by virtue of their high cellular plasticity. Evidence suggests that cancer stem cells acquire a multi-potent plastic phenotype and show vasculogenic potential. In this study, we report that glioblastoma stem-like cells (GSCs) can form vasculogenic mimicry in tumor xenografts and express pro-vascular molecules. We isolated GSCs from resected human glioblastoma tissues and demonstrated their stemness, differentiation, and in vivo tumor-initiating potential. Through a limiting dilution assay, CD133+ (CD133(+)-GSC) and CD133- (CD133(-)-GSC) subpopulation of GSCs were obtained. Orthotopic xenotransplantation study revealed that these two subpopulations of GSCs shared similar efficacy in tumor formation but showed distinct intratumor vasculature. In comparison with CD133(-)-GSC, a highly vascularized anaplastic tumor, mimicking vasculogenic mimicry, was found in CD133(+)-GSC-derived tumor xenografts. Subsets of CD133(+)-GSC but not CD133(-)-GSC were capable of vascular smooth muscle-like cell differentiation, in vitro and in vivo. In tumor xenografts, endothelium-associated CD31 gene was detected in implanted CD133(-)-GSC and exclusively dispersed within the tumor tissues. Although the detailed action mechanisms required further investigation, this study demonstrated the vasculogenic capacity of brain GSCs and their cellular plasticity. The results of expression of pro-vascular molecules and differentiation of vascular-like cells suggest that GSCs may contribute to form vessel-like structures and provide a blood supply for glioblastoma cells.
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PMID:CD133+ glioblastoma stem-like cells induce vascular mimicry in vivo. 2167 58

Over the past several decades, a tube formation assay using growth factor-reduced Matrigel has been typically employed to demonstrate the angiogenic activity of vascular endothelial cells in vitro. However, recently growing evidence has shown that this assay is not limited to test vascular behavior for endothelial cells. Instead, it also has been used to test the ability of a number of tumor cells to develop a vascular phenotype. This capability was consistent with their vasculogenic behavior identified in xenotransplanted animals, a process known as vasculogenic mimicry (VM). There is a multitude of evidence demonstrating that tumor cell-mediated VM plays a vital role in the tumor development, independent of endothelial cell angiogenesis. For example, tumor cells were found to participate in the blood perfused, vascular channel formation in tissue samples from melanoma and glioblastoma patients. Here, we described this tubular network assay as a useful tool in evaluation of vasculogenic activity of tumor cells. We found that some tumor cell lines such as melanoma B16F1 cells, glioblastoma U87 cells, and breast cancer MDA-MB-435 cells are able to form vascular tubules; but some do not such as colon cancer HCT116 cells. Furthermore, this vascular phenotype is dependent on cell numbers plated on the Matrigel. Therefore, this assay may serve as powerful utility to screen the vascular potential of a variety of cell types including vascular cells, tumor cells as well as other cells.
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PMID:A Matrigel-based tube formation assay to assess the vasculogenic activity of tumor cells. 2193 Dec 89

Angiogenesis is an important process for the cell growth of normal and tumor tissues. Vasculogenic mimicry (VM) is a newly described vascular network structure that was first described in aggressive melanomas. To find out whether VM also exists in astrocytomas and to examine its clinical significance, we studied 80 malignant astrocytoma samples using immunohistochemistry coupled with periodic acid-Schiff (PAS) staining. To explore the possible therapeutic methods of anti-VM formation, we cultured astrocytoma cells using three-dimensional Matrigel and investigated the effects of Endostar, an endothelial cell growth inhibitor, on astrocytoma cell growth, invasion, and VM formation. VM structures were found in 8 samples of malignant astrocytomas, seven of which were grade IV astrocytomas. Glioblastoma U251 cells cultured in Matrigel formed vessel-like loops and networks, mimicking the features of VM in vivo, whereas such structures were not found in cultured normal astrocytes or well-differentiated astrocytoma SHG44 cells. In addition, treatment with Endostar led to a dose- and time-dependent inhibition of proliferation and invasion of both U251and SHG44 cells, but VM formation by U251 cells in vitro was not prominently affected. In conclusion, VM is frequently detected in aggressive glioblastomas, and the presence of VM may constitute a new predictor for poor prognosis in astrocytoma patients. Although Endostar has broad anti-tumor effects due to anti-angiogenesis and anti-tumor cell mechanisms, its inhibitory effects on VM formation by U251cells in vitro are not remarkable.
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PMID:Demonstration of vasculogenic mimicry in astrocytomas and effects of Endostar on U251 cells. 2194 Jan 12


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