Abstract
BackgroundTargeting tumor angiogenesis and vasculature is a promising strategy for the inhibition of tumor growth and dissemination. Evidence suggests that tumor vasculature expresses unique markers that distinguish it from normal vasculature. Our efforts focused on the molecular characterization of endothelial cells (EC) in the search for selective markers of tumor vasculature that might be helpful for the development of effective therapeutic approaches.ResultsWe investigated by microarray analysis the gene expression profiles of EC purified and cultured from tumor (ovarian carcinoma [HOC-EC]) and normal (human adrenal gland [HA-EC]) tissue specimens. We found distinct transcriptional features characterizing the EC of different origin, and identified 158 transcripts highly expressed by HOC-EC. We analyzed four of these genes, ADAM23, FAP, GPNMB and PRSS3, which were not previously known to be expressed by endothelium. In vitro experiments confirmed the higher expression of the selected genes in tumor-derived endothelium with no expression in tumor cells. In vivo investigation by in situ hybridization established that ADAM23, GPNMB and PRSS3 expression is localized on blood vessels of human cancer specimens.ConclusionThese findings elucidate some of the molecular features of the tumor endothelium. Comparative transcriptomic analysis allowed us to determine molecular differences of tumor and normal tissue-derived endothelium and to identify novel markers that might be exploited to selectively target tumor vasculature.
Highlights
Targeting tumor angiogenesis and vasculature is a promising strategy for the inhibition of tumor growth and dissemination
Characterization of Endothelial Cells (EC) isolated from human specimens Endothelial cells were reproducibly isolated from human tissue specimens: HOC-endothelial cells (EC) from ovarian carcinoma, HKC-EC from kidney carcinoma, HA-EC from adrenal gland and HSk-EC from skin
Endothelial cell cultures typically created a homogeneous monolayer of elongated cells in close contact and maintained an uniform morphology after few passages in culture; they formed capillary-like cord structures when plated on matrigel
Summary
Targeting tumor angiogenesis and vasculature is a promising strategy for the inhibition of tumor growth and dissemination. Our efforts focused on the molecular characterization of endothelial cells (EC) in the search for selective markers of tumor vasculature that might be helpful for the development of effective therapeutic approaches. Tumor-induced vessels are ultrastructurally abnormal and differ from normal vasculature. They lack functional pericytes and are unusually permeable [6]. These abnormalities reflect the pathological nature of their induction, and underpin the novel therapeutic strategies directed against the vascular elements of the tumor stroma to selectively affect tumor vasculature and inhibit tumor growth [7]
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