Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors
The clinical benefit conferred by vascular endothelial growth factors (VEGF)-targeted therapies is variable, and tumors from treated patients eventually reinitiate growth. Here, we identify a glycosylation-dependent pathway that compensates for the absence of cognate ligand and preserves angiogenesi...
Guardado en:
Autores principales: | , , , , , , , , , , , , , , , |
---|---|
Formato: | JOUR |
Materias: | |
Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_00928674_v156_n4_p744_Croci |
Aporte de: |
id |
todo:paper_00928674_v156_n4_p744_Croci |
---|---|
record_format |
dspace |
spelling |
todo:paper_00928674_v156_n4_p744_Croci2023-10-03T14:55:21Z Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors Croci, D.O. Cerliani, J.P. Dalotto-Moreno, T. Méndez-Huergo, S.P. Mascanfroni, I.D. Dergan-Dylon, S. Toscano, M.A. Caramelo, J.J. García-Vallejo, J.J. Ouyang, J. Mesri, E.A. Junttila, M.R. Bais, C. Shipp, M.A. Salatino, M. Rabinovich, G.A. Angiogenesis Inhibitors Animals Anoxia Endothelial Cells Galectin 1 Glycosylation Humans Mice Neoplasms Neovascularization, Pathologic Receptors, Mitogen Vascular Endothelial Growth Factors galectin 1 lectin receptor ligand sialic acid vasculotropin vasculotropin antibody vasculotropin receptor 2 angiogenesis animal experiment animal model animal tissue Article breast metastasis cancer inhibition controlled study depletion drug efficacy endothelium cell gene silencing glycosylation human human cell hypoxia immunocompetent cell kidney carcinoma liver cell carcinoma metastatic colorectal cancer mouse neoplasm non small cell lung cancer nonhuman protein binding protein secretion vascularization The clinical benefit conferred by vascular endothelial growth factors (VEGF)-targeted therapies is variable, and tumors from treated patients eventually reinitiate growth. Here, we identify a glycosylation-dependent pathway that compensates for the absence of cognate ligand and preserves angiogenesis in response to VEGF blockade. Remodeling of the endothelial cell (EC) surface glycome selectively regulated binding of galectin-1 (Gal1), which upon recognition of complex N-glycans on VEGFR2, activated VEGF-like signaling. Vessels within anti-VEGF-sensitive tumors exhibited high levels of α2-6-linked sialic acid, which prevented Gal1 binding. In contrast, anti-VEGF refractory tumors secreted increased Gal1 and their associated vasculature displayed glycosylation patterns that facilitated Gal1-EC interactions. Interruption of β1-6GlcNAc branching in ECs or silencing of tumor-derived Gal1 converted refractory into anti-VEGF-sensitive tumors, whereas elimination of α2-6-linked sialic acid conferred resistance to anti-VEGF. Disruption of the Gal1-N-glycan axis promoted vascular remodeling, immune cell influx and tumor growth inhibition. Thus, targeting glycosylation-dependent lectin-receptor interactions may increase the efficacy of anti-VEGF treatment. PaperFlick © 2014 Elsevier Inc. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00928674_v156_n4_p744_Croci |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
Angiogenesis Inhibitors Animals Anoxia Endothelial Cells Galectin 1 Glycosylation Humans Mice Neoplasms Neovascularization, Pathologic Receptors, Mitogen Vascular Endothelial Growth Factors galectin 1 lectin receptor ligand sialic acid vasculotropin vasculotropin antibody vasculotropin receptor 2 angiogenesis animal experiment animal model animal tissue Article breast metastasis cancer inhibition controlled study depletion drug efficacy endothelium cell gene silencing glycosylation human human cell hypoxia immunocompetent cell kidney carcinoma liver cell carcinoma metastatic colorectal cancer mouse neoplasm non small cell lung cancer nonhuman protein binding protein secretion vascularization |
spellingShingle |
Angiogenesis Inhibitors Animals Anoxia Endothelial Cells Galectin 1 Glycosylation Humans Mice Neoplasms Neovascularization, Pathologic Receptors, Mitogen Vascular Endothelial Growth Factors galectin 1 lectin receptor ligand sialic acid vasculotropin vasculotropin antibody vasculotropin receptor 2 angiogenesis animal experiment animal model animal tissue Article breast metastasis cancer inhibition controlled study depletion drug efficacy endothelium cell gene silencing glycosylation human human cell hypoxia immunocompetent cell kidney carcinoma liver cell carcinoma metastatic colorectal cancer mouse neoplasm non small cell lung cancer nonhuman protein binding protein secretion vascularization Croci, D.O. Cerliani, J.P. Dalotto-Moreno, T. Méndez-Huergo, S.P. Mascanfroni, I.D. Dergan-Dylon, S. Toscano, M.A. Caramelo, J.J. García-Vallejo, J.J. Ouyang, J. Mesri, E.A. Junttila, M.R. Bais, C. Shipp, M.A. Salatino, M. Rabinovich, G.A. Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors |
topic_facet |
Angiogenesis Inhibitors Animals Anoxia Endothelial Cells Galectin 1 Glycosylation Humans Mice Neoplasms Neovascularization, Pathologic Receptors, Mitogen Vascular Endothelial Growth Factors galectin 1 lectin receptor ligand sialic acid vasculotropin vasculotropin antibody vasculotropin receptor 2 angiogenesis animal experiment animal model animal tissue Article breast metastasis cancer inhibition controlled study depletion drug efficacy endothelium cell gene silencing glycosylation human human cell hypoxia immunocompetent cell kidney carcinoma liver cell carcinoma metastatic colorectal cancer mouse neoplasm non small cell lung cancer nonhuman protein binding protein secretion vascularization |
description |
The clinical benefit conferred by vascular endothelial growth factors (VEGF)-targeted therapies is variable, and tumors from treated patients eventually reinitiate growth. Here, we identify a glycosylation-dependent pathway that compensates for the absence of cognate ligand and preserves angiogenesis in response to VEGF blockade. Remodeling of the endothelial cell (EC) surface glycome selectively regulated binding of galectin-1 (Gal1), which upon recognition of complex N-glycans on VEGFR2, activated VEGF-like signaling. Vessels within anti-VEGF-sensitive tumors exhibited high levels of α2-6-linked sialic acid, which prevented Gal1 binding. In contrast, anti-VEGF refractory tumors secreted increased Gal1 and their associated vasculature displayed glycosylation patterns that facilitated Gal1-EC interactions. Interruption of β1-6GlcNAc branching in ECs or silencing of tumor-derived Gal1 converted refractory into anti-VEGF-sensitive tumors, whereas elimination of α2-6-linked sialic acid conferred resistance to anti-VEGF. Disruption of the Gal1-N-glycan axis promoted vascular remodeling, immune cell influx and tumor growth inhibition. Thus, targeting glycosylation-dependent lectin-receptor interactions may increase the efficacy of anti-VEGF treatment. PaperFlick © 2014 Elsevier Inc. |
format |
JOUR |
author |
Croci, D.O. Cerliani, J.P. Dalotto-Moreno, T. Méndez-Huergo, S.P. Mascanfroni, I.D. Dergan-Dylon, S. Toscano, M.A. Caramelo, J.J. García-Vallejo, J.J. Ouyang, J. Mesri, E.A. Junttila, M.R. Bais, C. Shipp, M.A. Salatino, M. Rabinovich, G.A. |
author_facet |
Croci, D.O. Cerliani, J.P. Dalotto-Moreno, T. Méndez-Huergo, S.P. Mascanfroni, I.D. Dergan-Dylon, S. Toscano, M.A. Caramelo, J.J. García-Vallejo, J.J. Ouyang, J. Mesri, E.A. Junttila, M.R. Bais, C. Shipp, M.A. Salatino, M. Rabinovich, G.A. |
author_sort |
Croci, D.O. |
title |
Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors |
title_short |
Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors |
title_full |
Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors |
title_fullStr |
Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors |
title_full_unstemmed |
Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors |
title_sort |
glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-vegf refractory tumors |
url |
http://hdl.handle.net/20.500.12110/paper_00928674_v156_n4_p744_Croci |
work_keys_str_mv |
AT crocido glycosylationdependentlectinreceptorinteractionspreserveangiogenesisinantivegfrefractorytumors AT cerlianijp glycosylationdependentlectinreceptorinteractionspreserveangiogenesisinantivegfrefractorytumors AT dalottomorenot glycosylationdependentlectinreceptorinteractionspreserveangiogenesisinantivegfrefractorytumors AT mendezhuergosp glycosylationdependentlectinreceptorinteractionspreserveangiogenesisinantivegfrefractorytumors AT mascanfroniid glycosylationdependentlectinreceptorinteractionspreserveangiogenesisinantivegfrefractorytumors AT dergandylons glycosylationdependentlectinreceptorinteractionspreserveangiogenesisinantivegfrefractorytumors AT toscanoma glycosylationdependentlectinreceptorinteractionspreserveangiogenesisinantivegfrefractorytumors AT caramelojj glycosylationdependentlectinreceptorinteractionspreserveangiogenesisinantivegfrefractorytumors AT garciavallejojj glycosylationdependentlectinreceptorinteractionspreserveangiogenesisinantivegfrefractorytumors AT ouyangj glycosylationdependentlectinreceptorinteractionspreserveangiogenesisinantivegfrefractorytumors AT mesriea glycosylationdependentlectinreceptorinteractionspreserveangiogenesisinantivegfrefractorytumors AT junttilamr glycosylationdependentlectinreceptorinteractionspreserveangiogenesisinantivegfrefractorytumors AT baisc glycosylationdependentlectinreceptorinteractionspreserveangiogenesisinantivegfrefractorytumors AT shippma glycosylationdependentlectinreceptorinteractionspreserveangiogenesisinantivegfrefractorytumors AT salatinom glycosylationdependentlectinreceptorinteractionspreserveangiogenesisinantivegfrefractorytumors AT rabinovichga glycosylationdependentlectinreceptorinteractionspreserveangiogenesisinantivegfrefractorytumors |
_version_ |
1782023825515347968 |