|Endosialin: A novel malignant cell therapeutic target for neuroblastoma|
Authors: Cecile Rouleau, Robert Smale, Jose Sancho, Yao-Shi Fu, Leslie Kurtzberg, William Weber, Ariel Kruger, Craig Jones, Stephanie Roth, Christy Bormann, Sarah Dunham, Roy Krumbholz, Maritza Curiel, Gina Wallar, James Mascarello, Juanita Campos-Rivera, Bruce Horten, Steven Schmid, Glenn Miller, Beverly A. Teicher
Affiliations: Genzyme Corp., 49 New York Avenue, Framingham, MA 01701, USA, Developmental Therapeutics Program, National Cancer Institute, 6130 Executive Boulevard, Rockville, MD 20852, USA
Published online on: Monday, June 20, 2011
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 neuroendocrine 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.