PUBLICATION
Identification of CD90 as a putative cancer stem cell marker and therapeutic target in insulinomas
- Authors
- Buishand, F.O., Arkesteijn, G.J., Feenstra, L., Oorsprong, C., Mestemaker, M., Starke, A., Speel, E.J., Kirpensteijn, J., Mol, J.
- ID
- ZDB-PUB-160407-6
- Date
- 2016
- Source
- Stem cells and development 25(11): 826-35 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Biomarkers, Tumor/metabolism*
- Carcinogenesis/drug effects
- Carcinogenesis/pathology
- Cell Line, Tumor
- Doxorubicin/pharmacology
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/metabolism
- Flow Cytometry
- Gangliosides/metabolism
- Gene Expression Regulation/drug effects
- Humans
- Immunohistochemistry
- Insulinoma/metabolism*
- Insulinoma/therapy*
- Mice, Nude
- Molecular Targeted Therapy*
- Neoplastic Stem Cells/drug effects
- Neoplastic Stem Cells/metabolism*
- Thy-1 Antigens/metabolism*
- Xenograft Model Antitumor Assays
- Zebrafish/embryology
- Zebrafish/metabolism
- PubMed
- 27049037 Full text @ Stem Cells Dev.
Citation
Buishand, F.O., Arkesteijn, G.J., Feenstra, L., Oorsprong, C., Mestemaker, M., Starke, A., Speel, E.J., Kirpensteijn, J., Mol, J. (2016) Identification of CD90 as a putative cancer stem cell marker and therapeutic target in insulinomas. Stem cells and development. 25(11):826-35.
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 intra-tumoral 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. .
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping