title: Nucleolin expressed at the cell surface is a marker of endothelial cells in angiogenic blood vessels.
abstract: A tumor-homing peptide, F3, selectively binds to endothelial cells in tumor blood vessels and to tumor cells. Here, we show that the cell surface molecule recognized by F3 is nucleolin. Nucleolin specifically bound to an F3 peptide affinity matrix from extracts of cultured breast carcinoma cells. Antibodies and cell surface biotin labeling revealed nucleolin at the surface of actively growing cells, and these cells bound and internalized fluorescein-conjugated F3 peptide, transporting it into the nucleus. In contrast, nucleolin was exclusively nuclear in serum-starved cells, and F3 did not bind to these cells. The binding and subsequent internalization of F3 were blocked by an antinucleolin antibody. Like the F3 peptide, intravenously injected antinucleolin antibodies selectively accumulated in tumor vessels and in angiogenic vessels of implanted "matrigel" plugs. These results show that cell surface nucleolin is a specific marker of angiogenic endothelial cells within the vasculature. It may be a useful target molecule for diagnostic tests and drug delivery applications.
authors.affiliation: Cancer Research Center, The Burnham Institute, La Jolla, CA 92037-3198, USA.
authors.forename: Sven
authors.initials: S
authors.lastname: Christian
authors.forename: Jan
authors.initials: J
authors.lastname: Pilch
authors.forename: Maria E
authors.initials: ME
authors.lastname: Akerman
authors.forename: Kimmo
authors.initials: K
authors.lastname: Porkka
authors.forename: Pirjo
authors.initials: P
authors.lastname: Laakkonen
authors.forename: Erkki
authors.initials: E
authors.lastname: Ruoslahti
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000502:physiology; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use; D000954:Antigens, Surface / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001808:Blood Vessels / Q000166:cytology / Q000378:metabolism; D001943:Breast Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D000939:Epitopes / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000097796:Nucleolin
chemical_list: D000906:Antibodies; D000954:Antigens, Surface; D014408:Biomarkers, Tumor; D016895:Culture Media, Serum-Free; D000939:Epitopes; D006497:Heparan Sulfate; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D000097796:Nucleolin; C455179:F3 epitope