1,721,072 research outputs found
Characterization of endothelial cells isolated by human meningiomas.
No full textBACKGROUND: Meningiomas are common neoplasms of central nervous system characterized by a prominent angiogenesis in some histological subtypes and in some phase of their progression. Angiogenesis is a required event for the progression of solid tumor. However there are increasing evidences that the biological features of endothelial cells in the tumor other than the microvessel number dictate the behavior of cancer disease. In the present study we have tested the hypothesis that in vitro endothelial cells originated by human meningiomas have a different phenotype from that of normal capillary endothelial. METHODS: To isolate endothelial cells we have used a new technical approach principally based on collagenase digestion of the tissues followed by capture of endothelial cells obtained through molecules recognizing specific endothelial markers conjugated to magnetic beads. RESULTS: By using beads conjugated with a monoclonal antibody anti CD-36 we have separated with high efficiency and purity meningioma endothelial cells and established three cell cultures. These cells uptake acetylated LDL and express CD-31, CD-36, nitric oxide synthase type III, von Willebrand factor, which are specific markers of endothelial cells. Their mitogenic and motogenic potential in resting conditions or after stimulation with vascular endothelial growth factor-A is superimposable to that of normal capillary endothelial cells. However meningioma endothelial cells produce higher amount of interleukin-6 and of monocyte chemotactic peptide-1 than control cells. CONCLUSIONS: The establishment of a new and suitable technique to isolate endothelial cells from human cancers can be useful to learn more on angiogenic mechanisms in tumor progression. Furthermore, the data shown underline the possible pathogenic role in meningioma progression of infiltrating macrophages triggered by monocyte chemotactic peptide-1 released by tumor endothelial cells.
Nitric oxide modulates the angiogenic phenotype of middle-T transformed endothelial cells.
No full textThe role of nitric oxide (NO) in the induction of angiogenesis was evaluated in a murine heart endothelioma cell line (H.end.FB) carrying the mT oncogene. Two clonal derivatives of H.end.FB, H80 and H73, exhibiting different NO synthase (NOS) activities were selected and used in the study. The relationship among NOS activity and tumor cell behaviour (growth, and angiogenic capacity) and the molecular control of gene expression were investigated. H.end.FB and H80 on one side and H73 on the other side exhibited the highest and lowest NOS activity, respectively. Cell growth was inversely correlated to the amount of NO produced by the cell lines. Conversely, in the avascular rabbit cornea assay, H.end.FB and H80 cells were strongly angiogenic, while H73 were poorly angiogenic, indicating that the ability of the cells to induce neovascularization was associated with the extent of NO produced. Consistently, systemic administration to rabbits of the NOS inhibitor N(w)-nitro-L-arginine methyl ester (L-NAME) significantly reduced the angiogenicity of H.end.FB cells. RT-PCR evidenced that H.end.FB expressed mRNA for TGF-beta1 and all VEGF isoforms, VEGF165 being predominantly expressed. NOS inhibition reduced the basal expression of VEGF isoforms, while it markedly potentiated TGF-beta1 expression. These results indicate that the endogenous production of NO in tumor cells can serve as an autocrine/paracrine signalling mechanism of progression, by controlling angiogenic factor/modulator expressio
BIOCHEMICAL AND FUNCTIONAL CHARACTERIZATION OF THE INTERACTION OF GREMLIN (Drm) WITH HEPARIN/HEPARAN SULFATE PROTEOGLYCANS
No full textRole of VEGFR2 co-receptors in the modulation of the pro-angiogenic activity of gremlin.
No full text
Involvement of α(v)β (3) integrin in gremlin-induced angiogenesis.
No full textα(v)β(3) integrin modulates pro-angiogenic endothelial cell (EC) responses following vascular endothelial growth factor receptor-2 (VEGFR2) engagement. The bone morphogenic protein antagonist gremlin is a novel non-canonical VEGFR2 ligand that promotes the acquisition of a pro-angiogenic phenotype in ECs. Here we investigated the role of α(v)β(3) and extracellular matrix components on EC activation induced by gremlin. Gremlin triggers VEGFR2 phosphorylation and cell motility in ECs adherent to the α(v)β(3) ligand fibrinogen but not in ECs adherent to type-I collagen or fibronectin. Also, gremlin and VEGF-A stimulate the formation of VEGFR2/α(v)β(3) integrin complexes as shown by co-immunoprecipitation experiments and fluorescence resonance energy transfer analysis of β(3)-ECFP/VEGFR2-EYFP co-transfected ECs. Accordingly, anti-β(3) antibodies block the angiogenic activity exerted by gremlin or VEGF-A in vitro, ex vivo and in vivo. The results demonstrate a non-redundant role for α(v)β(3) in gremlin-induced angiogenesis and emphasize its contribution to the formation of functional multi-molecular VEGFR2 complexes responsible for the neovascularization events triggered by canonical and non-canonical pro-angiogenic VEGFR2 ligands
Gremlin as a novel pro-angiogenic VEGFR2 agonist: production of a biologically active recombinant form in S2 Drosophila cells
No full text
exploiting surface plasmon resonance technology for the identification of fibroblast growth factor 2 (FGF2) antagonists endowed with antiangiogenic activity
No full text- …
