TY - JOUR
T1 - Identification of CD90 as Putative Cancer Stem Cell Marker and Therapeutic Target in Insulinomas
AU - Buishand, Floryne O.
AU - Arkesteijn, Ger J. A.
AU - Feenstra, Laurien R.
AU - Oorsprong, Claire W. D.
AU - Mestemaker, Margiet
AU - Starke, Achim
AU - Speel, Ernst-Jan M.
AU - Kirpensteijn, Jolle
AU - Mol, Jan A.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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.
AB - 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.
U2 - 10.1089/scd.2016.0032
DO - 10.1089/scd.2016.0032
M3 - Article
C2 - 27049037
SN - 1547-3287
VL - 25
SP - 826
EP - 835
JO - Stem Cells and Development
JF - Stem Cells and Development
IS - 11
ER -