Bioavailability of VEGF in tumor-shed vesicles depends on vesicle burst induced by acidic pH 1

Giulia Taraboletti, Sandra D'Ascenzo, Ilaria Giusti, Daniela Marchetti, Patrizia Borsotti, Danilo Millimaggi, Raffaella Giavazzi, Antonio Pavan, Vincenza Dolo

Research output: Contribution to journalArticlepeer-review


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 CABA I 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 tumor microenvironment) 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.

Original languageEnglish
Pages (from-to)96-103
Number of pages8
JournalNeoplasia (United States)
Issue number2
Publication statusPublished - Feb 2006


  • Ovarian cancer
  • pH
  • Shed membrane vesicles
  • Tumor angiogenesis
  • VEGF

ASJC Scopus subject areas

  • Cancer Research


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