Vascular endothelial growth factor-165 overexpression stimulates angiogenesis and induces cyst formation and macrophage infiltration in human ovarian cancer xenografts

Monique C A Duyndam, Marion C G W Hilhorst, Hennie M M Schlüper, Henk M W Verheul, Paul J. Van Diest, Georg Kraal, Herbert M. Pinedo, Epie Boven

Research output: Contribution to journalArticle

Abstract

Vascular endothelial growth factor (VEGF) is suggested to be an important regulator of angiogenesis in ovarian cancer. We have evaluated the effects of VEGF overexpression on the histology and growth rate of human ovarian cancer xenografts. OVCAR-3 human ovarian cancer cells were stably transfected with an expression vector encoding the 165-amino acid isoform of VEGF. As subcutaneous xenografts, moderately and highly VEGF165-overexpressing OVCAR-3 cells formed tumors with large cysts. Immunohistochemistry demonstrated an increase in the number of CD31-positive microvessels, some of which were larger in diameter than those in the parental tumors, as well as extensive vascular rimming around the cysts. Weakly VEGF165-overexpressing tumors also contained an increased number of CD31-positive microvessels and occasional vascular rimming, but cysts were not present. Immunohistochemistry further revealed the presence of monocytes and macrophages in both parental and VEGF165-overexpressing xenografts. Interestingly, the number of monocytes/macrophages was greatly increased in moderately and highly VEGF165-overexpressing xenografts and large areas populated with monocytes/macrophages were detected within the tumor stroma. Although the higher number of CD31-positive cells would suggest a better vascularization pattern in VEGF165-overexpressing xenografts, tumor growth rates were not increased when compared with that of parental xenografts. These data provide functional evidence for a role of VEGF165 in cyst formation and monocyte/macrophage infiltration.

Original languageEnglish (US)
Pages (from-to)537-548
Number of pages12
JournalAmerican Journal of Pathology
Volume160
Issue number2
StatePublished - 2002
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Duyndam, M. C. A., Hilhorst, M. C. G. W., Schlüper, H. M. M., Verheul, H. M. W., Van Diest, P. J., Kraal, G., Pinedo, H. M., & Boven, E. (2002). Vascular endothelial growth factor-165 overexpression stimulates angiogenesis and induces cyst formation and macrophage infiltration in human ovarian cancer xenografts. American Journal of Pathology, 160(2), 537-548.