Identification of CD90 as Putative Cancer Stem Cell Marker and Therapeutic Target in Insulinomas

Floryne O Buishand, Ger J A Arkesteijn, Laurien R Feenstra, Claire W D Oorsprong, Margiet Mestemaker, Achim Starke, Ernst-Jan M Speel, Jolle Kirpensteijn, Jan A Mol

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)826-35
Number of pages10
JournalStem Cells and Development
Volume25
Issue number11
Early online date6 Apr 2016
DOIs
Publication statusPublished - 1 Jun 2016

Keywords

  • Animals
  • Biomarkers, Tumor
  • Carcinogenesis
  • Cell Line, Tumor
  • Doxorubicin
  • Embryo, Nonmammalian
  • Flow Cytometry
  • Gangliosides
  • Gene Expression Regulation
  • Humans
  • Immunohistochemistry
  • Insulinoma
  • Mice, Nude
  • Molecular Targeted Therapy
  • Neoplastic Stem Cells
  • Thy-1 Antigens
  • Xenograft Model Antitumor Assays
  • Zebrafish
  • Journal Article
  • Research Support, Non-U.S. Gov't

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