Gene expression of tumor angiogenesis dissected: specific targeting of colon cancer angiogenic vasculature.
Crucial to designing angiostatic and vascular targeting agents is the identification of target molecules. Because angiogenesis is not limited to pathologic conditions, careful evaluation of putative therapeutic targets is warranted to prevent adverse effects associated with impaired physiologic angiogenesis. To identify tumor-specific angiogenesis markers, we compared transcriptional profiles of angiogenic endothelial cells isolated from malignant and nonmalignant tissues with those of resting endothelial cells. We identified 17 genes that showed specific overexpression in tumor endothelium but not in angiogenic endothelium of normal tissues, creating a therapeutic window for tumor vasculature-specific targeting. Antibody targeting of 4 cell-surface-expressed or secreted products (vimentin, CD59, HMGB1, IGFBP7) inhibited angiogenesis in vitro and in vivo. Finally, targeting endothelial vimentin in a mouse tumor model significantly inhibited tumor growth and reduced microvessel density. Our results demonstrate the usefulness of the identification and subsequent targeting of specific tumor endothelial markers for anticancer therapy.
van Beijnum
Judy R
JR
Angiogenesis Laboratory, Department of Pathology, University Hospital Maastricht, PO Box 5800, 6202AZ Maastricht, The Netherlands.
Dings
Ruud P
RP
van der Linden
Edith
E
Zwaans
Bernadette M M
BM
Ramaekers
Frans C S
FC
Mayo
Kevin H
KH
Griffioen
Arjan W
AW
D000818:Animals; D002642:Chick Embryo; D003110:Colonic Neoplasms / Q000098:blood supply* / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008833:Microcirculation; D009389:Neovascularization, Pathologic; D009693:Nucleic Acid Hybridization; D014471:Umbilical Veins / Q000166:cytology; D014746:Vimentin / Q000378:metabolism
D014746:Vimentin