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.

Lung cancer stem cells—origin, characteristics and therapy

“…Another important cell surface marker is the CD90 that are highly expressed in lung cancer cells (62). A recent study discovered that CD90 is specifically expressed by CSCs of insulinomas which makes it an ideal therapeutic target for treatment of insulinoma (63). Another effective target could be CD47, a transmembrane protein which is seen in almost all solid tumors .Novel CSC based treatment will reach the above mentioned targets by using their respective antibodies against them (64).…”

Evaluation of Accessory Lacrimal Gland in Muller’s Muscle Conjunctival Resection Specimens for Precursor Cell Markers and Biological Markers of Dry Eye Disease

“…Although we chose to focus on nestin 26,27 , ABCG2 29,53 and CD90 54,55 as epithelial progenitor cell markers based on our evaluation of the available literature and negative results with (CD9, CD29, CD81, CD105) there are a number of other potential markers CD44 27 and PDX-1 28 which could be investigated further. This study is the first to demonstrate the presence of a population of cells in adult ALG tissue expressing precursor markers.…”

Dasatinib inhibition of cSRC prevents the migration and metastasis of canine mammary cancer cells with enhanced Wnt and HER signalling

“…To investigate the effect of inhibition of cSRC or PI3K signalling on the metastasis of canine mammary cells, a xenograft model in zebrafish was used that has been validated previously and has been used in our laboratory to investigate the metastasis of canine insulinoma cells . The transgenic zebrafish line Tg(fli1:GFP) (a generous gift from Brant M. Weinstein, PhD, National Institutes of Health) was used for the xenograft experiments.…”

“…Dechorionized 2‐day‐post‐fertilization zebrafish embryos were anaesthetised with 0.003% tricaine (Sigma‐Aldrich) and positioned on a 10‐cm Petri dish coated with 1% agarose. Single cell suspensions of CMT‐U27‐RED (pHAGE2‐EF1a‐DsRed‐PuroR) cells were resuspended in 2% polyvinylpyrrolidone (Sigma‐Aldrich) in Hank's balanced salt solution (200 cells/nL) and were implanted within 1 hour, as reported previously . The zebrafish embryos were either injected with 2 nL CMT‐U27 RED cell suspension or with 2 nL CMT‐U27 RED cell suspension containing 10 μM dasatinib or 10 μM everolimus.…”

“…However, cells may also be inserted directly into the blood stream through injection into the duct of Cuvier to investigate metastatic properties of breast cancer cell lines . This model has also been validated in our laboratory for human insulinoma cell line metastasis and compared to xenografts in mice . The same model was used for investigating the effects of mTOR and cSRC inhibition on the metastatic properties of cells with high Wnt signalling in the current study.…”