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Sanyukta Rana - One of the best experts on this subject based on the ideXlab platform.
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combined evaluation of a panel of protein and mirna serum Exosome biomarkers for pancreatic cancer diagnosis increases sensitivity and specificity
International Journal of Cancer, 2015Co-Authors: Bindhu Madhavan, Sanyukta Rana, Shijing Yue, Uwe Galli, Wolfgang Gross, Miryam Muller, Nathalia A Giese, Holger Kalthoff, T Becker, Markus W BuchlerAbstract:Late diagnosis contributes to pancreatic cancer (PaCa) dismal prognosis, urging for reliable, early detection. Serum-Exosome protein and/or miRNA markers might be suitable candidates, which we controlled for patients with PaCa. Protein markers were selected according to expression in Exosomes of PaCa cell line culture supernatants, but not healthy donors' serum-Exosomes. miRNA was selected according to abundant recovery in microarrays of patients with PaCa, but not healthy donors' serum-Exosomes and Exosome-depleted serum. According to these preselections, serum-Exosomes were tested by flow cytometry for the PaCa-initiating cell (PaCIC) markers CD44v6, Tspan8, EpCAM, MET and CD104. Serum-Exosomes and Exosome-depleted serum was tested for miR-1246, miR-4644, miR-3976 and miR-4306 recovery by qRT-PCR. The majority (95%) of patients with PaCa (131) and patients with nonPa-malignancies reacted with a panel of anti-CD44v6, -Tspan8, -EpCAM and -CD104. Serum-Exosomes of healthy donors' and patients with nonmalignant diseases were not reactive. Recovery was tumor grading and staging independent including early stages. The selected miR-1246, miR-4644, miR-3976 and miR-4306 were significantly upregulated in 83% of PaCa serum-Exosomes, but rarely in control groups. These miRNA were also elevated in Exosome-depleted serum of patients with PaCa, but at a low level. Concomitant evaluation of PaCIC and miRNA serum-Exosome marker panels significantly improved sensitivity (1.00, CI: 0.95-1) with a specificity of 0.80 (CI: 0.67-0.90) for PaCa versus all others groups and of 0.93 (CI: 0.81-0.98) excluding nonPa-malignancies. Thus, the concomitant evaluation of PaCIC and PaCa-related miRNA marker panels awaits retrospective analyses of larger cohorts, as it should allow for a highly sensitive, minimally-invasive PaCa diagnostics.
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toward tailored Exosomes the exosomal tetraspanin web contributes to target cell selection
The International Journal of Biochemistry & Cell Biology, 2012Co-Authors: Sanyukta Rana, Daniela Stadel, Margot ZollerAbstract:Abstract Exosomes are discussed as potent therapeutics due to efficient transfer of proteins, mRNA and miRNA in selective targets. However, therapeutic Exosome application requires knowledge on target structures to avoid undue delivery. Previous work suggesting exosomal tetraspanin–integrin complexes to be involved in target cell binding, we aimed to control this hypothesis and to define target cell ligands. Exosomes are rich in tetraspanins that associate besides other molecules with integrins. Co-immunoprecipitation of Exosome lysates from rat tumor lines that differ only with respect to Tspan8 and beta4 revealed promiscuity of tetraspanin–integrin associations, but also few preferential interactions like that of Tspan8 with alpha4 and beta4 integrin chains. These minor differences in exosomal tetraspanin-complexes strongly influence target cell selection in vitro and in vivo, efficient Exosome-uptake being seen in hematopoietic cells and solid organs. Exosomes expressing the Tspan8–alpha4 complex are most readily taken up by endothelial and pancreas cells, CD54 serving as a major ligand. Selectivity of uptake was confirmed with Exosomes from an alpha4 cDNA transfected Tspan8+ lymph node stroma line. Distinct from Exosomes from the parental line, the latter preferentially targeted endothelial cells and in vivo the pancreas. Importantly, pulldown experiments provided strong evidence that Exosome-uptake occurs in internalization-prone membrane domains. This is the first report on the exosomal tetraspanin web contributing to target cell selection such that predictions can be made on potential targets, which will facilitate tailoring Exosomes for drug delivery.
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cell surface tetraspanin tspan8 contributes to molecular pathways of Exosome induced endothelial cell activation
Cancer Research, 2010Co-Authors: Irina Nazarenko, Sanyukta Rana, Alexandra Baumann, Jessica Mcalear, Andrea Hellwig, Michael Trendelenburg, Gunter Lochnit, Klaus T Preissner, Margot ZollerAbstract:Tumor-derived Exosomes containing the tetraspanin Tspan8 can efficiently induce angiogenesis in tumors and tumor-free tissues. However, little information exists on Exosome-endothelial cell (EC) interactions or the proangiogenic role of tetraspanins, which are a constitutive component of Exosomes. In this study, we used a rat adenocarcinoma model (AS-Tspan8) to explore the effects of exosomal Tspan8 on angiogenesis. Tspan8 contributed to a selective recruitment of proteins and mRNA into Exosomes, including CD106 and CD49d, which were implicated in Exosome-EC binding and EC internalization. We found that EC internalized Tspan8-CD49d complex-containing Exosomes. Exosome uptake induced vascular endothelial growth factor (VEGF)-independent regulation of several angiogenesis-related genes, including von Willebrand factor, Tspan8, chemokines CXCL5 and MIF, chemokine receptor CCR1, and, together with VEGF, VEGF receptor 2. EC uptake of Tspan8-CD49d complex-containing Exosomes was accompanied by enhanced EC proliferation, migration, sprouting, and maturation of EC progenitors. Unraveling these new pathways of Exosome-initiated EC regulation could provide new options for therapeutic interference with tumor-induced angiogenesis.
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cell surface tetraspanin tspan8 contributes to molecular pathways of Exosome induced endothelial cell activation
Cancer Research, 2010Co-Authors: Irina Nazarenko, Sanyukta Rana, Andrea Hellwig, Michael Trendelenburg, Alexandra Auma, Jessica Mcalea, Gunte Lochni, Klaus T Preissne, Margo ZolleAbstract:Tumor-derived Exosomes containing the tetraspanin Tspan8 can efficiently induce angiogenesis in tumors and tumor-free tissues. However, little information exists on Exosome-endothelial cell (EC) interactions or the proangiogenic role of tetraspanins, which are a constitutive component of Exosomes. In this study, we used a rat adenocarcinoma model (AS-Tspan8) to explore the effects of exosomal Tspan8 on angiogenesis. Tspan8 contributed to a selective recruitment of proteins and mRNA into Exosomes, including CD106 and CD49d, which were implicated in Exosome-EC binding and EC internalization. We found that EC internalized Tspan8-CD49d complex-containing Exosomes. Exosome uptake induced vascular endothelial growth factor (VEGF)-independent regulation of several angiogenesis-related genes, including von Willebrand factor, Tspan8, chemokines CXCL5 and MIF, chemokine receptor CCR1, and, together with VEGF, VEGF receptor 2. EC uptake of Tspan8-CD49d complex-containing Exosomes was accompanied by enhanced EC proliferation, migration, sprouting, and maturation of EC progenitors. Unraveling these new pathways of Exosome-initiated EC regulation could provide new options for therapeutic interference with tumor-induced angiogenesis.
Margot Zoller - One of the best experts on this subject based on the ideXlab platform.
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toward tailored Exosomes the exosomal tetraspanin web contributes to target cell selection
The International Journal of Biochemistry & Cell Biology, 2012Co-Authors: Sanyukta Rana, Daniela Stadel, Margot ZollerAbstract:Abstract Exosomes are discussed as potent therapeutics due to efficient transfer of proteins, mRNA and miRNA in selective targets. However, therapeutic Exosome application requires knowledge on target structures to avoid undue delivery. Previous work suggesting exosomal tetraspanin–integrin complexes to be involved in target cell binding, we aimed to control this hypothesis and to define target cell ligands. Exosomes are rich in tetraspanins that associate besides other molecules with integrins. Co-immunoprecipitation of Exosome lysates from rat tumor lines that differ only with respect to Tspan8 and beta4 revealed promiscuity of tetraspanin–integrin associations, but also few preferential interactions like that of Tspan8 with alpha4 and beta4 integrin chains. These minor differences in exosomal tetraspanin-complexes strongly influence target cell selection in vitro and in vivo, efficient Exosome-uptake being seen in hematopoietic cells and solid organs. Exosomes expressing the Tspan8–alpha4 complex are most readily taken up by endothelial and pancreas cells, CD54 serving as a major ligand. Selectivity of uptake was confirmed with Exosomes from an alpha4 cDNA transfected Tspan8+ lymph node stroma line. Distinct from Exosomes from the parental line, the latter preferentially targeted endothelial cells and in vivo the pancreas. Importantly, pulldown experiments provided strong evidence that Exosome-uptake occurs in internalization-prone membrane domains. This is the first report on the exosomal tetraspanin web contributing to target cell selection such that predictions can be made on potential targets, which will facilitate tailoring Exosomes for drug delivery.
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cell surface tetraspanin tspan8 contributes to molecular pathways of Exosome induced endothelial cell activation
Cancer Research, 2010Co-Authors: Irina Nazarenko, Sanyukta Rana, Alexandra Baumann, Jessica Mcalear, Andrea Hellwig, Michael Trendelenburg, Gunter Lochnit, Klaus T Preissner, Margot ZollerAbstract:Tumor-derived Exosomes containing the tetraspanin Tspan8 can efficiently induce angiogenesis in tumors and tumor-free tissues. However, little information exists on Exosome-endothelial cell (EC) interactions or the proangiogenic role of tetraspanins, which are a constitutive component of Exosomes. In this study, we used a rat adenocarcinoma model (AS-Tspan8) to explore the effects of exosomal Tspan8 on angiogenesis. Tspan8 contributed to a selective recruitment of proteins and mRNA into Exosomes, including CD106 and CD49d, which were implicated in Exosome-EC binding and EC internalization. We found that EC internalized Tspan8-CD49d complex-containing Exosomes. Exosome uptake induced vascular endothelial growth factor (VEGF)-independent regulation of several angiogenesis-related genes, including von Willebrand factor, Tspan8, chemokines CXCL5 and MIF, chemokine receptor CCR1, and, together with VEGF, VEGF receptor 2. EC uptake of Tspan8-CD49d complex-containing Exosomes was accompanied by enhanced EC proliferation, migration, sprouting, and maturation of EC progenitors. Unraveling these new pathways of Exosome-initiated EC regulation could provide new options for therapeutic interference with tumor-induced angiogenesis.
Irina Nazarenko - One of the best experts on this subject based on the ideXlab platform.
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cell surface tetraspanin tspan8 contributes to molecular pathways of Exosome induced endothelial cell activation
Cancer Research, 2010Co-Authors: Irina Nazarenko, Sanyukta Rana, Alexandra Baumann, Jessica Mcalear, Andrea Hellwig, Michael Trendelenburg, Gunter Lochnit, Klaus T Preissner, Margot ZollerAbstract:Tumor-derived Exosomes containing the tetraspanin Tspan8 can efficiently induce angiogenesis in tumors and tumor-free tissues. However, little information exists on Exosome-endothelial cell (EC) interactions or the proangiogenic role of tetraspanins, which are a constitutive component of Exosomes. In this study, we used a rat adenocarcinoma model (AS-Tspan8) to explore the effects of exosomal Tspan8 on angiogenesis. Tspan8 contributed to a selective recruitment of proteins and mRNA into Exosomes, including CD106 and CD49d, which were implicated in Exosome-EC binding and EC internalization. We found that EC internalized Tspan8-CD49d complex-containing Exosomes. Exosome uptake induced vascular endothelial growth factor (VEGF)-independent regulation of several angiogenesis-related genes, including von Willebrand factor, Tspan8, chemokines CXCL5 and MIF, chemokine receptor CCR1, and, together with VEGF, VEGF receptor 2. EC uptake of Tspan8-CD49d complex-containing Exosomes was accompanied by enhanced EC proliferation, migration, sprouting, and maturation of EC progenitors. Unraveling these new pathways of Exosome-initiated EC regulation could provide new options for therapeutic interference with tumor-induced angiogenesis.
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cell surface tetraspanin tspan8 contributes to molecular pathways of Exosome induced endothelial cell activation
Cancer Research, 2010Co-Authors: Irina Nazarenko, Sanyukta Rana, Andrea Hellwig, Michael Trendelenburg, Alexandra Auma, Jessica Mcalea, Gunte Lochni, Klaus T Preissne, Margo ZolleAbstract:Tumor-derived Exosomes containing the tetraspanin Tspan8 can efficiently induce angiogenesis in tumors and tumor-free tissues. However, little information exists on Exosome-endothelial cell (EC) interactions or the proangiogenic role of tetraspanins, which are a constitutive component of Exosomes. In this study, we used a rat adenocarcinoma model (AS-Tspan8) to explore the effects of exosomal Tspan8 on angiogenesis. Tspan8 contributed to a selective recruitment of proteins and mRNA into Exosomes, including CD106 and CD49d, which were implicated in Exosome-EC binding and EC internalization. We found that EC internalized Tspan8-CD49d complex-containing Exosomes. Exosome uptake induced vascular endothelial growth factor (VEGF)-independent regulation of several angiogenesis-related genes, including von Willebrand factor, Tspan8, chemokines CXCL5 and MIF, chemokine receptor CCR1, and, together with VEGF, VEGF receptor 2. EC uptake of Tspan8-CD49d complex-containing Exosomes was accompanied by enhanced EC proliferation, migration, sprouting, and maturation of EC progenitors. Unraveling these new pathways of Exosome-initiated EC regulation could provide new options for therapeutic interference with tumor-induced angiogenesis.
Margo Zolle - One of the best experts on this subject based on the ideXlab platform.
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cell surface tetraspanin tspan8 contributes to molecular pathways of Exosome induced endothelial cell activation
Cancer Research, 2010Co-Authors: Irina Nazarenko, Sanyukta Rana, Andrea Hellwig, Michael Trendelenburg, Alexandra Auma, Jessica Mcalea, Gunte Lochni, Klaus T Preissne, Margo ZolleAbstract:Tumor-derived Exosomes containing the tetraspanin Tspan8 can efficiently induce angiogenesis in tumors and tumor-free tissues. However, little information exists on Exosome-endothelial cell (EC) interactions or the proangiogenic role of tetraspanins, which are a constitutive component of Exosomes. In this study, we used a rat adenocarcinoma model (AS-Tspan8) to explore the effects of exosomal Tspan8 on angiogenesis. Tspan8 contributed to a selective recruitment of proteins and mRNA into Exosomes, including CD106 and CD49d, which were implicated in Exosome-EC binding and EC internalization. We found that EC internalized Tspan8-CD49d complex-containing Exosomes. Exosome uptake induced vascular endothelial growth factor (VEGF)-independent regulation of several angiogenesis-related genes, including von Willebrand factor, Tspan8, chemokines CXCL5 and MIF, chemokine receptor CCR1, and, together with VEGF, VEGF receptor 2. EC uptake of Tspan8-CD49d complex-containing Exosomes was accompanied by enhanced EC proliferation, migration, sprouting, and maturation of EC progenitors. Unraveling these new pathways of Exosome-initiated EC regulation could provide new options for therapeutic interference with tumor-induced angiogenesis.
Andrea Hellwig - One of the best experts on this subject based on the ideXlab platform.
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cell surface tetraspanin tspan8 contributes to molecular pathways of Exosome induced endothelial cell activation
Cancer Research, 2010Co-Authors: Irina Nazarenko, Sanyukta Rana, Alexandra Baumann, Jessica Mcalear, Andrea Hellwig, Michael Trendelenburg, Gunter Lochnit, Klaus T Preissner, Margot ZollerAbstract:Tumor-derived Exosomes containing the tetraspanin Tspan8 can efficiently induce angiogenesis in tumors and tumor-free tissues. However, little information exists on Exosome-endothelial cell (EC) interactions or the proangiogenic role of tetraspanins, which are a constitutive component of Exosomes. In this study, we used a rat adenocarcinoma model (AS-Tspan8) to explore the effects of exosomal Tspan8 on angiogenesis. Tspan8 contributed to a selective recruitment of proteins and mRNA into Exosomes, including CD106 and CD49d, which were implicated in Exosome-EC binding and EC internalization. We found that EC internalized Tspan8-CD49d complex-containing Exosomes. Exosome uptake induced vascular endothelial growth factor (VEGF)-independent regulation of several angiogenesis-related genes, including von Willebrand factor, Tspan8, chemokines CXCL5 and MIF, chemokine receptor CCR1, and, together with VEGF, VEGF receptor 2. EC uptake of Tspan8-CD49d complex-containing Exosomes was accompanied by enhanced EC proliferation, migration, sprouting, and maturation of EC progenitors. Unraveling these new pathways of Exosome-initiated EC regulation could provide new options for therapeutic interference with tumor-induced angiogenesis.
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cell surface tetraspanin tspan8 contributes to molecular pathways of Exosome induced endothelial cell activation
Cancer Research, 2010Co-Authors: Irina Nazarenko, Sanyukta Rana, Andrea Hellwig, Michael Trendelenburg, Alexandra Auma, Jessica Mcalea, Gunte Lochni, Klaus T Preissne, Margo ZolleAbstract:Tumor-derived Exosomes containing the tetraspanin Tspan8 can efficiently induce angiogenesis in tumors and tumor-free tissues. However, little information exists on Exosome-endothelial cell (EC) interactions or the proangiogenic role of tetraspanins, which are a constitutive component of Exosomes. In this study, we used a rat adenocarcinoma model (AS-Tspan8) to explore the effects of exosomal Tspan8 on angiogenesis. Tspan8 contributed to a selective recruitment of proteins and mRNA into Exosomes, including CD106 and CD49d, which were implicated in Exosome-EC binding and EC internalization. We found that EC internalized Tspan8-CD49d complex-containing Exosomes. Exosome uptake induced vascular endothelial growth factor (VEGF)-independent regulation of several angiogenesis-related genes, including von Willebrand factor, Tspan8, chemokines CXCL5 and MIF, chemokine receptor CCR1, and, together with VEGF, VEGF receptor 2. EC uptake of Tspan8-CD49d complex-containing Exosomes was accompanied by enhanced EC proliferation, migration, sprouting, and maturation of EC progenitors. Unraveling these new pathways of Exosome-initiated EC regulation could provide new options for therapeutic interference with tumor-induced angiogenesis.