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Identification of CD90 as Putative Cancer Stem Cell Marker and Therapeutic Target in Insulinomas
Floryne O Buishand1, Ger J A Arkesteijn2, Laurien R Feenstra1
11 Faculty of Veterinary Medicine, Department of Clinical Sciences of Companion Animals, Utrecht University , Utrecht, The Netherlands .
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.
Insights
Targeting cancer stem cells (CSCs) in malignant insulinoma (INS) may improve outcomes. This study identified CD90 as a marker for INS CSCs, showing anti-CD90 antibodies reduced tumor cell viability and metastasis.
Area of Science:
- Endocrinology
- Oncology
- Cancer Stem Cell Biology
Background:
- Malignant insulinoma (INS) has a poor long-term prognosis following surgical resection.
- The development of novel adjuvant therapies targeting cancer stem cells (CSCs) is crucial for improving patient outcomes.
- Identifying and characterizing specific CSC markers in INS is essential for therapeutic development.
Purpose of the Study:
- To characterize and target putative cancer stem cells (CSCs) in malignant insulinoma (INS).
- To evaluate the therapeutic potential of targeting identified CSC markers in preclinical models.
Main Methods:
- Fluorescence-activated cell sorting (FACS) was used to screen human INS and pancreatic carcinoid cell lines for stem cell markers.
- In vivo tumor-initiating potential was assessed using athymic nude mice xenografts.
- The efficacy of anti-CD90 monoclonal antibodies was evaluated in a zebrafish embryo INS xenograft model.
- Immunohistochemistry was employed to detect CD90 expression in primary INS tumors.
Main Results:
- CD90, CD166, and GD2 were identified as potential CSC markers in INS cell lines.
- CD90-positive (CD90(+)) INS cells exhibited significantly increased tumor-initiating potential in vivo.
- Anti-CD90 monoclonal antibodies reduced the viability and metastatic potential of INS cells in zebrafish xenografts.
- Primary INS tumors showed CD90 expression, along with positive staining in intratumoral fibroblasts and vascular endothelium.
Conclusions:
- CD90 represents a potential therapeutic target for malignant insulinoma (INS) CSCs.
- Anti-CD90 monoclonal antibodies show promise as a novel adjuvant therapy for INS, potentially by targeting INS cells or the tumor microenvironment.
- Targeting CD90 may offer a new strategy to improve the prognosis of malignant insulinoma.
