Circulating plasma vascular endothelial growth factor in mice bearing human ovarian carcinoma xenograft correlates with tumor progression and response to therapy

Luigi Manenti, Elena Riccardi, Sergio Marchini, Elitza Naumova, Irene Floriani, Angela Garofalo, Romina Dossi, Eleonora Marrazzo, Domenico Ribatti, Eugenio Scanziani, Maria Rosa Bani, Dorina Belotti, Massimo Broggini, Raffaella Giavazzi

Research output: Contribution to journalArticlepeer-review

Abstract

Vascular endothelial growth factor (VEGF) performs as an angiogenic and permeability factor in ovarian cancer, and its overexpression has been associated with poor prognosis. However, models to study its role as a marker of tumor progression are lacking. We generated xenograft variants derived from the A2780 human ovarian carcinoma (1A9), stably transfected with VEGF121 in sense (1A9-VS-1) and antisense orientation (1A9-VAS-3). 1A9, 1A9-VS-1, and 1A9-VAS-3 disseminated in the peritoneal cavity of nude mice, but only 1A9-VS-1, the VEGF121-overexpressing tumor variant, produced ascites. Tumor biopsies from 1A9-VS-1 showed alterations in the vascular pattern and caused an angiogenic response in the chorioallantoic membrane assay. A significant level of soluble VEGF was detectable in the plasma of mice bearing 1A9-VS-1 even at an early stage of tumor growth. Plasma VEGF correlated positively with tumor burden in the peritoneal cavity and ascites accumulation. Cisplatin reduced the tumor burden and ascites in mice bearing 1A9-VS-1; the response was associated with a significant decrease of VEGF in plasma. This 1A9-VS-1 xenograft model reproduces the behavior of human ovarian cancer by growing in the peritoneal cavity, being highly malignant, and producing ascites. Plasma VEGF as a marker of tumor progression offers a valuable means of detecting early tumor response and following up treatments in an animal model.

Original languageEnglish
Pages (from-to)715-725
Number of pages11
JournalMolecular Cancer Therapeutics
Volume4
Issue number5
DOIs
Publication statusPublished - May 2005

ASJC Scopus subject areas

  • Oncology
  • Drug Discovery
  • Pharmacology

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