title: Identification of novel vascular markers through gene expression profiling of tumor-derived endothelium.
abstract: BACKGROUND
  Targeting 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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Laboratory of Biology and Treatment of Metastases, Mario Negri Institute for Pharmacological Research, Milano, Italy. cghilardi@marionegri.it
authors.forename: Carmen
authors.initials: C
authors.lastname: Ghilardi
authors.forename: Giovanna
authors.initials: G
authors.lastname: Chiorino
authors.forename: Romina
authors.initials: R
authors.lastname: Dossi
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Nagy
authors.forename: Raffaella
authors.initials: R
authors.lastname: Giavazzi
authors.forename: MariaRosa
authors.initials: M
authors.lastname: Bani
mesh_terms: D051722:ADAM Proteins / Q000235:genetics; D000311:Adrenal Glands / Q000098:blood supply / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D010450:Endopeptidases; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D018093:Gelatinases; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008565:Membrane Proteins; D009369:Neoplasms / Q000098:blood supply* / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics; D014357:Trypsin / Q000235:genetics; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D051722:ADAM Proteins; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D010450:Endopeptidases; D018093:Gelatinases; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D014357:Trypsin; D000099167:Fibroblast Activation Protein Alpha; C503042:GPNMB protein, human; C040749:PRSS3 protein, human; C114633:ADAM23 protein, human