title: Endosialin protein expression and therapeutic target potential in human solid tumors: sarcoma versus carcinoma.
abstract: OBJECTIVE
  Endosialin/CD248/tumor endothelial marker 1 is expressed in stromal cells, endothelial cells, and pericytes in various tumors; however, few studies have focused on expression in malignant cells.
  
  
  METHODS
  We studied expression of endosialin in clinical specimens, cell culture, and animal models and designed an anti-endosialin therapeutic prototype.
  
  
  RESULTS
  Fifty human tumor cell lines and 6 normal cell types in culture were assayed by reverse transcription-PCR and/or flow cytometry for endosialin. Cell surface protein was found on 7 sarcoma lines, 1 neuroblastoma, and 4 normal cell types in culture. A fully human anti-endosialin antibody bound to human A-673 Ewing's sarcoma cells and SK-N-AS neuroblastoma cells but not HT-1080 cells. Exposure of cells to an anti-human IgG conjugated to saporin resulted in growth inhibition only of endosialin-expressing cells. Endosialin expression was assessed by immunohistochemistry in 250 clinical specimens of human cancer including 20 cancer subtypes. Endosialin is frequently found in human cancers. Endosialin expression is mainly a perivascular feature in carcinomas, with some expression in stromal cells. In sarcomas, endosialin is expressed by malignant cells, perivascular cells, and stromal cells. Development and characterization of experimental models for studying endosialin biology in sarcomas and evaluating anti-endosialin therapies is presented.
  
  
  CONCLUSIONS
  Findings suggest that an anti-endosialin immunotoxin might be a promising therapeutic approach for endosialin-positive neoplasia, especially synovial sarcoma, fibrosarcoma, malignant fibrous histiocytoma, liposarcoma, and osteosarcoma. Thus, a diagnostic/therapeutic targeted therapeutic approach to treatment of endosialin-expressing tumors may be possible.
authors.affiliation: Genzyme Corporation, Framingham, Massachusetts 01701, USA. Cecile.Rouleau@Genzyme.com
authors.forename: Cecile
authors.initials: C
authors.lastname: Rouleau
authors.forename: Maritza
authors.initials: M
authors.lastname: Curiel
authors.forename: William
authors.initials: W
authors.lastname: Weber
authors.forename: Robert
authors.initials: R
authors.lastname: Smale
authors.forename: Leslie
authors.initials: L
authors.lastname: Kurtzberg
authors.forename: James
authors.initials: J
authors.lastname: Mascarello
authors.forename: Carol
authors.initials: C
authors.lastname: Berger
authors.forename: Gina
authors.initials: G
authors.lastname: Wallar
authors.forename: Rebecca
authors.initials: R
authors.lastname: Bagley
authors.forename: Nakayuki
authors.initials: N
authors.lastname: Honma
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Isao
authors.initials: I
authors.lastname: Ishida
authors.forename: Shiro
authors.initials: S
authors.lastname: Kataoka
authors.forename: Beth L
authors.initials: BL
authors.lastname: Thurberg
authors.forename: Khodadad
authors.initials: K
authors.lastname: Mehraein
authors.forename: Bruce
authors.initials: B
authors.lastname: Horten
authors.forename: Glenn
authors.initials: G
authors.lastname: Miller
authors.forename: Beverly A
authors.initials: BA
authors.lastname: Teicher
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007150:Immunohistochemistry; D000922:Immunotoxins / Q000494:pharmacology*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D054789:Ribosome Inactivating Proteins, Type 1 / Q000633:toxicity; D000076985:Saporins; D012509:Sarcoma / Q000235:genetics / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; C078203:CD248 protein, human; D007074:Immunoglobulin G; D000922:Immunotoxins; D012333:RNA, Messenger; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins