Blood vessels either form de novo through the process of vasculogenesis or through angiogenesis that involves the sprouting and proliferation of endothelial cells in pre-existing blood vessels. A complex interactive n...Blood vessels either form de novo through the process of vasculogenesis or through angiogenesis that involves the sprouting and proliferation of endothelial cells in pre-existing blood vessels. A complex interactive network of signaling cascades downstream from at least three of the nine known G-protein-coupled sphingosine-1-phosphate (S1P) receptors act as a prime effector of neovascularization that occurs in embryonic development and in association with various pathologies. This review focuses on the current knowledge of the roles of S1P signaling in vasculogenesis and angiogenesis, with particular emphasis on vascular cell adhesion and motility responses.展开更多
CD146 molecule, the surface marker of tumor vascular, plays a key role in the proliferation and migration of vascular endothelial cell. However, due to lack of suitable animal model,
Background Cellular repressor of ElA-stimulated genes(CREG) is homeostatic modulated gene,which regulate a number of cellular processes,including cell differentiation, motility and survival.Previous studies have demon...Background Cellular repressor of ElA-stimulated genes(CREG) is homeostatic modulated gene,which regulate a number of cellular processes,including cell differentiation, motility and survival.Previous studies have demonstrated that CREG was expressed in all three germ layers,suggesting that it might act as a vital regulator during embryonic developing.The aim of the present study was to investigate the role of CREG in an embryonic stem cell(ESC) differentiation model that recapitulates the developmental steps of vasculogenesis.Methods The ES cells were stably transfected either pCXN2-FLAG-CREG-IRES-EGFP plasmid or pDS1- shRNA-CREG plasmid to produce the CREG+/ES cells and CREG-siRNA/ES cells,respectively.Vasculogenesis was detected by whole mount immunostainings for CD31.Dil labeled acLDL staining assay was used to detect branching pseudopods in cultures in Matrigel.Real-time PCR and Western blot analysis were employed to determine expressions of VEGF and Flk-1.Results CREG +/ES-derived embryoid bodies(EBs) were found to form spontaneously a primitive vascular network after 6 days of differentiation.In contrast, wildtype EBs exhibit theirs vasculogenesis until 13 days of differentiation by whole mount immunostainings for CD31. CREG +/EBs developed more rapidly branching pseudopods at 9 days compared with that of wildtype EBs by Dil labeled acLDL staining assay.In contrast,CREG-siRNA/ES exhibits an undifferentiated morphogenesis associated with an increase in apoptotic cells in spite of being derived from LIF and feeder layers.Administration of CREG-siRNA/ES cells with recombinant CREG protein rescued the phenomena that CREG boosted vasculogenesis in a dose-dependent fasion. Mechanically,Real-time PCR and Western blot analysis revealed the expressions both VEGF and Flk-1 significantly in- creased in CREG+/EBs.Moreover,after treatment of CREG+ /EBs with neurtralizing antibody against VEGF,the rapid vasculogenesis was significantly repressed.Conclusions Our data strongely demonstrate that CREG play a pivotal role in accelerating vasculogenesis in development of ES cells. VEGF,as its important downstream effector,mediated this bio-function.展开更多
Objective: To observe whether there is evidence for vascular channel formation by osteosarcoma cellsin vitro and to illustrate mechanism of vasculogenic mimicry in osteosarcoma.Methods: Osteosarcoma cell lines (U-2OS)...Objective: To observe whether there is evidence for vascular channel formation by osteosarcoma cellsin vitro and to illustrate mechanism of vasculogenic mimicry in osteosarcoma.Methods: Osteosarcoma cell lines (U-2OS) were tested for their ability to form tubular networks in three-dimensional culture containing type I collagen. The structures of the tubular networks were observed under a phase contrast microscope and an electron microscope.Results: Observation under light microscopy and electron microscopy showed that high aggressive osteosarcoma cells line (U-2OS) formed networks containing channels when grown in three-dimensional culture containing type I collagen in the absence of endothelial cells or fibroblasts.Conclusion: These observations strongly suggest that aggressive osteosarcoma cells may generate vascular channels that facilitate tumor perfusion independent of tumor angiogenesis and have the ability of vasculogenic mimicry. Key words osteosarcoma cells line - vasculogenesis mimicry - angiogenesis - 3-dimensional cultures This study was supported in part by the National Natural Sciences Foundation of China (No. 30271314).展开更多
基金Supported by Grants from the United States Public Health Service/National Institutes of Health, No. HL080404, HL094883 (Argraves KM) and HL061873, HL095067 (Argraves WS)NIH Training Grant to Improve Cardiovascular Therapies HL007260 (Wilkerson BA)American Heart Association 10PRE3910006 (Wilkerson BA)
文摘Blood vessels either form de novo through the process of vasculogenesis or through angiogenesis that involves the sprouting and proliferation of endothelial cells in pre-existing blood vessels. A complex interactive network of signaling cascades downstream from at least three of the nine known G-protein-coupled sphingosine-1-phosphate (S1P) receptors act as a prime effector of neovascularization that occurs in embryonic development and in association with various pathologies. This review focuses on the current knowledge of the roles of S1P signaling in vasculogenesis and angiogenesis, with particular emphasis on vascular cell adhesion and motility responses.
文摘CD146 molecule, the surface marker of tumor vascular, plays a key role in the proliferation and migration of vascular endothelial cell. However, due to lack of suitable animal model,
文摘Background Cellular repressor of ElA-stimulated genes(CREG) is homeostatic modulated gene,which regulate a number of cellular processes,including cell differentiation, motility and survival.Previous studies have demonstrated that CREG was expressed in all three germ layers,suggesting that it might act as a vital regulator during embryonic developing.The aim of the present study was to investigate the role of CREG in an embryonic stem cell(ESC) differentiation model that recapitulates the developmental steps of vasculogenesis.Methods The ES cells were stably transfected either pCXN2-FLAG-CREG-IRES-EGFP plasmid or pDS1- shRNA-CREG plasmid to produce the CREG+/ES cells and CREG-siRNA/ES cells,respectively.Vasculogenesis was detected by whole mount immunostainings for CD31.Dil labeled acLDL staining assay was used to detect branching pseudopods in cultures in Matrigel.Real-time PCR and Western blot analysis were employed to determine expressions of VEGF and Flk-1.Results CREG +/ES-derived embryoid bodies(EBs) were found to form spontaneously a primitive vascular network after 6 days of differentiation.In contrast, wildtype EBs exhibit theirs vasculogenesis until 13 days of differentiation by whole mount immunostainings for CD31. CREG +/EBs developed more rapidly branching pseudopods at 9 days compared with that of wildtype EBs by Dil labeled acLDL staining assay.In contrast,CREG-siRNA/ES exhibits an undifferentiated morphogenesis associated with an increase in apoptotic cells in spite of being derived from LIF and feeder layers.Administration of CREG-siRNA/ES cells with recombinant CREG protein rescued the phenomena that CREG boosted vasculogenesis in a dose-dependent fasion. Mechanically,Real-time PCR and Western blot analysis revealed the expressions both VEGF and Flk-1 significantly in- creased in CREG+/EBs.Moreover,after treatment of CREG+ /EBs with neurtralizing antibody against VEGF,the rapid vasculogenesis was significantly repressed.Conclusions Our data strongely demonstrate that CREG play a pivotal role in accelerating vasculogenesis in development of ES cells. VEGF,as its important downstream effector,mediated this bio-function.
基金This study was supported in part by the National Natural Sciences Foundation of China(No.30271314).
文摘Objective: To observe whether there is evidence for vascular channel formation by osteosarcoma cellsin vitro and to illustrate mechanism of vasculogenic mimicry in osteosarcoma.Methods: Osteosarcoma cell lines (U-2OS) were tested for their ability to form tubular networks in three-dimensional culture containing type I collagen. The structures of the tubular networks were observed under a phase contrast microscope and an electron microscope.Results: Observation under light microscopy and electron microscopy showed that high aggressive osteosarcoma cells line (U-2OS) formed networks containing channels when grown in three-dimensional culture containing type I collagen in the absence of endothelial cells or fibroblasts.Conclusion: These observations strongly suggest that aggressive osteosarcoma cells may generate vascular channels that facilitate tumor perfusion independent of tumor angiogenesis and have the ability of vasculogenic mimicry. Key words osteosarcoma cells line - vasculogenesis mimicry - angiogenesis - 3-dimensional cultures This study was supported in part by the National Natural Sciences Foundation of China (No. 30271314).
