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Stem Cells Dev ; 25(11): 826-35, 2016 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-27049037

RESUMO

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.


Assuntos
Biomarcadores Tumorais/metabolismo , Insulinoma/metabolismo , Insulinoma/terapia , Terapia de Alvo Molecular , Células-Tronco Neoplásicas/metabolismo , Antígenos Thy-1/metabolismo , Animais , Carcinogênese/efeitos dos fármacos , Carcinogênese/patologia , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Citometria de Fluxo , Gangliosídeos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Camundongos Nus , Células-Tronco Neoplásicas/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo
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