title: Identification of CD90 as Putative Cancer Stem Cell Marker and Therapeutic Target in Insulinomas.
abstract: The long-term prognosis after surgical resection of malignant insulinoma (INS) is poor. Novel adjuvant therapies, specifically targeting cancer stem cells (CSCs), are warranted. Therefore, the goal of this study was to characterize and target putative INS CSCs. Using fluorescence-activated cell sorting, human INS cell line CM and pancreatic carcinoid cell line BON1 were screened for the presence of stem cell-associated markers. CD90, CD166, and GD2 were identified as potential CSC markers. Only CD90(+) INS cells had an increased tumor-initiating potential in athymic nude mice. Anti-CD90 monoclonal antibodies decreased the viability and metastatic potential of injected cells in a zebrafish embryo INS xenograft model. Primary INS stained positive for CD90 by immunohistochemistry, however also intratumoral fibroblasts and vascular endothelium showed positive staining. The results of this study suggest that anti-CD90 monoclonals form a potential novel adjuvant therapeutic modality by targeting either INS cells directly, or by targeting the INS microenvironment.
authors.affiliation: 1 Faculty of Veterinary Medicine, Department of Clinical Sciences of Companion Animals, Utrecht University , Utrecht, The Netherlands .
authors.forename: Floryne O
authors.initials: FO
authors.lastname: Buishand
authors.affiliation: 2 Flow Cytometry Unit, Faculty of Veterinary Medicine, Division of Immunology, Utrecht University , Utrecht, The Netherlands .
authors.forename: Ger J A
authors.initials: GJ
authors.lastname: Arkesteijn
authors.affiliation: 1 Faculty of Veterinary Medicine, Department of Clinical Sciences of Companion Animals, Utrecht University , Utrecht, The Netherlands .
authors.forename: Laurien R
authors.initials: LR
authors.lastname: Feenstra
authors.affiliation: 1 Faculty of Veterinary Medicine, Department of Clinical Sciences of Companion Animals, Utrecht University , Utrecht, The Netherlands .
authors.forename: Claire W D
authors.initials: CW
authors.lastname: Oorsprong
authors.affiliation: 1 Faculty of Veterinary Medicine, Department of Clinical Sciences of Companion Animals, Utrecht University , Utrecht, The Netherlands .
authors.forename: Margiet
authors.initials: M
authors.lastname: Mestemaker
authors.affiliation: 3 Department of Surgery, Lukas Krankenhaus GmbH, Neuss and Insulinoma and GEP-NET Tumor Center Neuss-Dusseldorf , Neuss, Germany .
authors.forename: Achim
authors.initials: A
authors.lastname: Starke
authors.affiliation: 4 Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center , Maastricht, The Netherlands .
authors.forename: Ernst-Jan M
authors.initials: EJ
authors.lastname: Speel
authors.affiliation: 1 Faculty of Veterinary Medicine, Department of Clinical Sciences of Companion Animals, Utrecht University , Utrecht, The Netherlands .
authors.forename: Jolle
authors.initials: J
authors.lastname: Kirpensteijn
authors.affiliation: 1 Faculty of Veterinary Medicine, Department of Clinical Sciences of Companion Animals, Utrecht University , Utrecht, The Netherlands .
authors.forename: Jan A
authors.initials: JA
authors.lastname: Mol
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D063646:Carcinogenesis / Q000187:drug effects / Q000473:pathology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D005732:Gangliosides / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D007340:Insulinoma / Q000378:metabolism* / Q000628:therapy*; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D018800:Thy-1 Antigens / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D005732:Gangliosides; D018800:Thy-1 Antigens; C019403:ganglioside, GD2; D004317:Doxorubicin