Bioavailability of VEGF in Tumor-Shed Vesicles Depends on Vesicle Burst Induced by Acidic pH
Tumor angiogenesis is regulated by a dynamic crosstalk between tumor cells and the host microenvironment. Because membrane vesicles shed by tumor cells are known to mediate several tumor—host interactions, we determined whether vesicles might also stimulate angiogenesis. Vesicles shed by human ovar...
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doaj-db6deeb5e84645ebad82eeab5f79fdb72020-11-25T00:14:46ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022006-02-01829610310.1593/neo.05583Bioavailability of VEGF in Tumor-Shed Vesicles Depends on Vesicle Burst Induced by Acidic pHGiulia Taraboletti0Sandra D'Ascenzoy1Ilaria Giusti2Daniela Marchetti3Patrizia Borsotti4Danilo Millimaggi5Raffaella Giavazzi6Antonio Pavan7Vincenza Dolo8Department of Oncology, Mario Negri Institute for Pharmacological Research, Bergamo, ItalyDepartment of Experimental Medicine, L'Aquila University, L'Aquila 67100, ItalyDepartment of Experimental Medicine, L'Aquila University, L'Aquila 67100, ItalyDepartment of Experimental Medicine, L'Aquila University, L'Aquila 67100, ItalyDepartment of Oncology, Mario Negri Institute for Pharmacological Research, Bergamo, ItalyDepartment of Experimental Medicine, L'Aquila University, L'Aquila 67100, ItalyDepartment of Oncology, Mario Negri Institute for Pharmacological Research, Bergamo, ItalyDepartment of Experimental Medicine, L'Aquila University, L'Aquila 67100, ItalyDepartment of Experimental Medicine, L'Aquila University, L'Aquila 67100, Italy Tumor angiogenesis is regulated by a dynamic crosstalk between tumor cells and the host microenvironment. Because membrane vesicles shed by tumor cells are known to mediate several tumor—host interactions, we determined whether vesicles might also stimulate angiogenesis. Vesicles shed by human ovarian carcinoma cell lines CABAI and A2780 stimulated the motility and invasiveness of endothelial cells in vitro. Enzyme-linked immunosorbent assay and Western blot analysis revealed relevant amounts of vascular endothelial growth factor (VEGF) and the two matrix metalloproteinases MMP-2 and MMP-9, but not fibroblast growth factor-2, contained in shed vesicles. An A2780 cell—derived clone transfected to overexpress VEGF shed the same amount of vesicles as did a control clone, but contained significantly more VEGF within the vesicles. Despite a greater amount of VEGF in vesicles of the overexpressing clone, vesicles of both clones stimulated endothelial cell motility to comparable levels, suggesting that VEGF was stored within the vesicle and was unavailable. Only following vesicle burst induced by acidic pH (a characteristic of the tumormicroenvironment) was VEGF released, leading to significantly higher stimulation of cell motility. Thus, tumor-shed membrane vesicles carry VEGF and release it in a bioactive form in conditions typical of the tumor microenvironment. http://www.sciencedirect.com/science/article/pii/S1476558606800187Shed membrane vesiclesVEGFtumor angiogenesispHovarian cancer |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Giulia Taraboletti Sandra D'Ascenzoy Ilaria Giusti Daniela Marchetti Patrizia Borsotti Danilo Millimaggi Raffaella Giavazzi Antonio Pavan Vincenza Dolo |
spellingShingle |
Giulia Taraboletti Sandra D'Ascenzoy Ilaria Giusti Daniela Marchetti Patrizia Borsotti Danilo Millimaggi Raffaella Giavazzi Antonio Pavan Vincenza Dolo Bioavailability of VEGF in Tumor-Shed Vesicles Depends on Vesicle Burst Induced by Acidic pH Neoplasia: An International Journal for Oncology Research Shed membrane vesicles VEGF tumor angiogenesis pH ovarian cancer |
author_facet |
Giulia Taraboletti Sandra D'Ascenzoy Ilaria Giusti Daniela Marchetti Patrizia Borsotti Danilo Millimaggi Raffaella Giavazzi Antonio Pavan Vincenza Dolo |
author_sort |
Giulia Taraboletti |
title |
Bioavailability of VEGF in Tumor-Shed Vesicles Depends on Vesicle Burst Induced by Acidic pH |
title_short |
Bioavailability of VEGF in Tumor-Shed Vesicles Depends on Vesicle Burst Induced by Acidic pH |
title_full |
Bioavailability of VEGF in Tumor-Shed Vesicles Depends on Vesicle Burst Induced by Acidic pH |
title_fullStr |
Bioavailability of VEGF in Tumor-Shed Vesicles Depends on Vesicle Burst Induced by Acidic pH |
title_full_unstemmed |
Bioavailability of VEGF in Tumor-Shed Vesicles Depends on Vesicle Burst Induced by Acidic pH |
title_sort |
bioavailability of vegf in tumor-shed vesicles depends on vesicle burst induced by acidic ph |
publisher |
Elsevier |
series |
Neoplasia: An International Journal for Oncology Research |
issn |
1476-5586 1522-8002 |
publishDate |
2006-02-01 |
description |
Tumor angiogenesis is regulated by a dynamic crosstalk between tumor cells and the host microenvironment. Because membrane vesicles shed by tumor cells are known to mediate several tumor—host interactions, we determined whether vesicles might also stimulate angiogenesis. Vesicles shed by human ovarian carcinoma cell lines CABAI and A2780 stimulated the motility and invasiveness of endothelial cells in vitro. Enzyme-linked immunosorbent assay and Western blot analysis revealed relevant amounts of vascular endothelial growth factor (VEGF) and the two matrix metalloproteinases MMP-2 and MMP-9, but not fibroblast growth factor-2, contained in shed vesicles. An A2780 cell—derived clone transfected to overexpress VEGF shed the same amount of vesicles as did a control clone, but contained significantly more VEGF within the vesicles. Despite a greater amount of VEGF in vesicles of the overexpressing clone, vesicles of both clones stimulated endothelial cell motility to comparable levels, suggesting that VEGF was stored within the vesicle and was unavailable. Only following vesicle burst induced by acidic pH (a characteristic of the tumormicroenvironment) was VEGF released, leading to significantly higher stimulation of cell motility. Thus, tumor-shed membrane vesicles carry VEGF and release it in a bioactive form in conditions typical of the tumor microenvironment.
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topic |
Shed membrane vesicles VEGF tumor angiogenesis pH ovarian cancer |
url |
http://www.sciencedirect.com/science/article/pii/S1476558606800187 |
work_keys_str_mv |
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