1,720,977 research outputs found
Pericyte deficiencies lead to aberrant tumor vascularizaton in the brain of the NG2 null mouse.
No full textTightly regulated crosstalk between endothelial cells and pericytes is required for formation and maintenance of functional blood vessels. When the NG2 proteoglycan is absent from pericyte surfaces, vascularization of syngeneic tumors growing in the C57B1/6 mouse brain is aberrant in several respects, resulting in retardation of tumor progression. In the NG2 null mouse brain, pericyte investment of the tumor vascular endothelium is reduced, causing deficiencies in both pericyte and endothelial cell maturation, as well as reduced basal lamina assembly. While part of this deficit may be due to the previously-identified role of NG2 in 51 integrin-dependent periyte/endothelial cell crosstalk, the ablation of NG2 also appears responsible for loss of collagen VI anchorage, in turn leading to reduced collagen IV deposition. Poor functionality of tumor vessels in NG2 null brain is reflected by reduced vessel patency and increased vessel leakiness, resulting in large increases in tumor hypoxia. These findings demonstrate the importance of NG2-dependent pericyte/endothelial cell interaction in the development and maturation of tumor blood vessels, identifying NG2 as a potential target for anti-angiogenic cancer therapy
NG2 proteoglycan confers drug resistance in leukemic cells through a novel drug transport-related mechanism
No full textReversal of the cellular roles in angiogenesis: implications for anti-angiogenic therapy
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Reversal of cellular roles in angiogenesis: implications for anti-angiogenic therapy
No full textWhether occurring during embryonic development, in pathophysiological conditions, such as
wound healing/tissue regeneration, or in fully pathological conditions, such as cancer and
inflammatory diseases, angiogenesis is traditionally thought to be a strongly endotheliumdriven
process. In fact, the main features of the angiogenic model, largely preserved as first
proposed by Folkman [1] in 1971, implicate endothelial cells as primary effectors of the
tubulogenesis process [2]. As depicted in figure 1a, pro-angiogenic growth factors (especially
VEGF) trigger endothelial cell activation, proliferation and motility. In addition to resident
endothelial cells, circulating endothelial precursors may also participate in the formation of
interconnected neotubules [3]. Another crucial role is played by local pericytes or bone
marrow-derived pericyte progenitors [4-6]. According to the angiogenesis dogma, pericytes
are recruited by migrating endothelial cells to confer stability to nascent vascular structures
[2,4-7]. Indeed, targeting pericytes through NG2 proteoglycan [8] or PDGFRβ [5,6] strongly
impacts neovasculogenesis and may also affect lymphangiogenesis
An intimate interplay between precocious, migrating pericytes and endothelial cells governs human fetal brain angiogenesis
No full textIn order to better understand the process of angiogenesis in the developing human brain, we have examined the spatial relationship and relative contributions of endothelial cells and pericytes, the two primary cell types involved in vessel growth, together with their relation with the vascular basement membrane. Pericytes were immunolocalized through use of the specific markers nerve/glial antigen 2 (NG2) proteoglycan, endosialin (CD248) and the platelet-derived growth factor receptor beta (PDGFR-beta), while endothelial cells were identified by the pan-endothelial marker CD31 and the blood brain barrier (BBB)-specific markers claudin-5 and glucose transporter isoform 1 (GLUT-1). The quantitative analysis demonstrates that microvessels of the fetal human telencephalon are characterized by a continuous layer of activated/angiogenic NG2 pericytes, which tightly invest endothelial cells and participate in the earliest stages of vessel growth. Immunolabelling with anti-active matrix metalloproteinase-2 (aMMP-2) and anti-collagen type IV antibodies revealed that aMMP-2 producing endothelial cells and pericytes are both associated with the vascular basement membrane during vessel sprouting. Detailed localization of the two vascular cell types during angiogenesis suggests that growing microvessels of the human telencephalon are formed by a pericyte-driven angiogenic process in which the endothelial cells are preceded and guided by migrating pericytes during organization of the growing vessel wall
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Identification of NG2 Proteoglycan-Collagen type VI Interplays as a Pro-Metastatic Factor in Soft-Tissue Sarcomas and Design of Approaches for the Exploitation of NG2 as an Immunotherapeutic Target
No full textTargeting the prognostic and metastasis-predicting surface proteoglycan for immunotherapeutic treatment of selected sarcomas
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