title: Reassessment of endothelin receptor A expression in normal and neoplastic human tissues using the novel rabbit monoclonal antibody UMB-8.
abstract: The endothelins ET-1, ET-2 and ET-3 are a family of peptides, which exert their actions via two G protein-coupled receptor subtypes, ETA and ETB. ET-1 is a potent vasoconstrictor and is involved in the development of different cardiovascular and renal disorders. Additionally, ET-1 and the ETA receptor have been shown to be important mediators of cancer growth and metastasis. We have extensively characterized the novel monoclonal rabbit anti-ETA antibody UMB-8 using transfected cells as well as mouse, rat and human tissues. UMB-8 was then tested in a large series of formalin-fixed and paraffin-embedded human normal and neoplastic tissue specimens. Specificity of UMB-8 was demonstrated by detection of a broad band migrating at 70-80kDa in Western blot analyses of ETA-transfected HEK-293 cells and of different mouse tissues and by agonist-dependent translocation of the immunosignal from the surface of ETA-transfected cells into the cytosol. In tissue samples, UMB-8 yielded an efficient immunostaining of distinct cell populations with a predominance of plasma membrane staining, which was abolished after preadsorption of the antibody with its immunizing peptide. In normal tissue, ETA was present in the heart, blood vessels, gut and kidneys. ETA was also detected with a hitherto unappreciated high prevalence in all types of sarcomas and in glioblastomas, but also in various epithelial tumor entities and in tumor stroma. All in all, UMB-8 may prove of great value in the identification of ETA-expressing tumors during routine histopathological examinations.
authors.affiliation: Institute of Pharmacology and Toxicology, Jena University Hospital, Friedrich Schiller University Jena, Drackendorfer Str. 1, D-07747 Jena, Germany. Electronic address: Amelie.Lupp@med.uni-jena.de.
authors.forename: Amelie
authors.initials: A
authors.lastname: Lupp
authors.affiliation: Institute of Pharmacology and Toxicology, Jena University Hospital, Friedrich Schiller University Jena, Drackendorfer Str. 1, D-07747 Jena, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Mann
authors.affiliation: Institute of Pharmacology and Toxicology, Jena University Hospital, Friedrich Schiller University Jena, Drackendorfer Str. 1, D-07747 Jena, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Heeb
authors.affiliation: Department of General and Visceral Surgery, Zentralklinik Bad Berka, Robert-Koch-Allee 9, 99437 Bad Berka, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kaemmerer
authors.affiliation: Laboratory of Pathology and Cytology Bad Berka, Robert-Koch-Allee 9, 99438 Bad Berka, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Sänger
authors.affiliation: Department of Pathology, Ernst-Moritz-Arndt-University Greifswald, Friedrich-Loeffler-Str. 23e, 17475 Greifswald, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Evert
authors.affiliation: Department of Pathology, Ernst-Moritz-Arndt-University Greifswald, Friedrich-Loeffler-Str. 23e, 17475 Greifswald, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Evert
authors.affiliation: Department of Neuropathology, Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Mawrin
authors.affiliation: Institute of Pharmacology and Toxicology, Jena University Hospital, Friedrich Schiller University Jena, Drackendorfer Str. 1, D-07747 Jena, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schulz
mesh_terms: D000911:Antibodies, Monoclonal / Q000378:metabolism*; D019332:Endothelin-1 / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009369:Neoplasms / Q000378:metabolism*; D044022:Receptor, Endothelin A / Q000378:metabolism*; D044023:Receptor, Endothelin B / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B
keywords: Antibody; Endothelin; Endothelin receptor A; Immunohistochemistry; Tumors