Circulating plasma vascular endothelial growth factor in mice bearing human ovarian carcinoma xenograft correlates with tumor progression and response to therapy.
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 VEGF(121) 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 VEGF(121)-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.
Manenti
Luigi
L
Laboratory of Biology and Therapy of Metastasis, Mario Negri Institute for Pharmacological Research, via Gavazzeni 11, 24125 Bergamo, Italy.
Riccardi
Elena
E
Marchini
Sergio
S
Naumova
Elitza
E
Floriani
Irene
I
Garofalo
Angela
A
Dossi
Romina
R
Marrazzo
Eleonora
E
Ribatti
Domenico
D
Scanziani
Eugenio
E
Bani
Mariarosa
M
Belotti
Dorina
D
Broggini
Massimo
M
Giavazzi
Raffaella
R
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001201:Ascites / Q000188:drug therapy / Q000473:pathology*; D049033:Chorioallantoic Membrane / Q000378:metabolism; D002945:Cisplatin / Q000627:therapeutic use; D016373:DNA, Antisense / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000235:genetics; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000556:secondary; D014183:Transplantation, Heterologous; D047368:Tumor Burden; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000097:blood*
D000970:Antineoplastic Agents; D016373:DNA, Antisense; D042461:Vascular Endothelial Growth Factor A; D002945:Cisplatin