Submitted February 16, 2006
Accepted May 16, 2006
Gene expression of tumor angiogenesis dissected; specific targeting of colon cancer angiogenic vasculature
Judy van Beijnum, Ruud P Dings, Edith van der Linden, Bernadette M Zwaans, Frans C Ramaekers, Kevin H Mayo, and Arjan W Griffioen*
Angiogenesis Laboratory, Department of Pathology, Maastricht University, Maastricht, The Netherlands
Department of Molecular Cell Biology, GROW, Maastricht University, The Netherlands
Department of Biochemistry, Molecular Biology & Biophysics,University of Minnesota, USA
* Corresponding author; email: aw.griffioen{at}path.unimaas.nl.
Crucial to designing angiostatic and vascular targeting agents is the identification of target molecules. Since angiogenesis is not limited to pathologies, careful evaluation of putative therapeutic targets is warranted to prevent side effects associated with impaired physiological angiogenesis. To identify tumor-specific angiogenesis markers, we compared transcriptional profiles of angiogenic endothelial cells isolated from both malignant and non-malignant tissues with that of resting endothelial cells. We identified 17 genes that show 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 four cell-surface expressed or secreted products (vimentin, CD59, HMGB1 and 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 utility of the identification and subsequent targeting of specific tumor endothelial markers for anticancer therapy.
