title: Endosialin: a novel malignant cell therapeutic target for neuroblastoma.
abstract: Endosialin emerged recently as a potential therapeutic target for sarcoma. Since some sarcoma subtypes, such as Ewing's sarcoma, show characteristics of neuroendocrine differentiation, we wondered whether cancers with neuro-endocrine properties and/or neuroectodermal origin, such as neuroblastoma, small cell lung cancer and melanoma, may express endosialin. Endosialin protein expression was surveyed in neuroblastoma, small cell lung cancer and melanoma in human clinical specimens by immunohistochemistry (IHC) and in human cell lines by flow cytometry. Side population cells were examined to determine whether cancer stem cells can express endosialin. Endosialin-expressing neuroblastoma cell lines were implanted in immunodeficient mice and allowed to grow. The xenograft tumors were resected and tested for endosialin expression by IHC. In human clinical specimens, vascular endosialin staining was observed in neuroblastoma, small cell lung cancer and melanoma. Malignant cell staining was strongest in neuroblastoma, weak in melanoma and rare in small cell lung cancer. In human cell lines, endosialin was detected in neuroblastoma cell lines, including cancer stem cell-like side population (SP) cells, but was absent in melanoma and was both rare and weak in small cell lung cancer. Human neuroblastoma xenograft tumors were found to be positive for endosialin. Our work suggests that endosialin may be a suitable therapeutic target for neuroblastoma.
authors.affiliation: Genzyme Corp., 49 New York Avenue, Framingham, MA 01701, USA.
authors.forename: Cecile
authors.initials: C
authors.lastname: Rouleau
authors.forename: Robert
authors.initials: R
authors.lastname: Smale
authors.forename: Jose
authors.initials: J
authors.lastname: Sancho
authors.forename: Yao-Shi
authors.initials: YS
authors.lastname: Fu
authors.forename: Leslie
authors.initials: L
authors.lastname: Kurtzberg
authors.forename: William
authors.initials: W
authors.lastname: Weber
authors.forename: Ariel
authors.initials: A
authors.lastname: Kruger
authors.forename: Craig
authors.initials: C
authors.lastname: Jones
authors.forename: Stephanie
authors.initials: S
authors.lastname: Roth
authors.forename: Christy
authors.initials: C
authors.lastname: Bormann
authors.forename: Sarah
authors.initials: S
authors.lastname: Dunham
authors.forename: Roy
authors.initials: R
authors.lastname: Krumbholz
authors.forename: Maritza
authors.initials: M
authors.lastname: Curiel
authors.forename: Gina
authors.initials: G
authors.lastname: Wallar
authors.forename: James
authors.initials: J
authors.lastname: Mascarello
authors.forename: Juanita
authors.initials: J
authors.lastname: Campos-Rivera
authors.forename: Bruce
authors.initials: B
authors.lastname: Horten
authors.forename: Steven
authors.initials: S
authors.lastname: Schmid
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 / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008175:Lung Neoplasms; D008545:Melanoma / Q000235:genetics / Q000378:metabolism; D051379:Mice; D058990:Molecular Targeted Therapy; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012509:Sarcoma / Q000235:genetics / Q000378:metabolism; D058985:Side-Population Cells / Q000378:metabolism; D055752:Small Cell Lung Carcinoma / Q000378:metabolism / Q000473:pathology; D014183:Transplantation, Heterologous
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; C078203:CD248 protein, human