High CD133 expression levels in gastrointestinal stromal tumors

Fabio Bozzi, Elena Conca, Giacomo Manenti, Tiziana Negri, Silvia Brich, Alessandro Gronchi, Marco A. Pierotti, Elena Tamborini, Silvana Pilotti

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Gastrointestinal stromal tumours (GISTs) have activating KIT or PDGFRA gene mutations. Imatinib mesylate, which targets KIT and PDGFRA, is effective in treating GISTs, but 90% of GIST patients become imatinib-resistant as a result of acquiring secondary KIT mutations. Recent findings suggest that tumour growth can be driven by mutated self-renewing progenitors known as cancer stem cells (CSCs), which are believed to be present in all neoplastic proliferations and are thought to accumulate mutations. It is therefore possible that the acquisition of secondary KIT mutations during imatinib treatment may occur in putative GIST CSCs. Methods: Using flow cytometry, in vivo murine xenografts and molecular characterization, we tried to identify putative GIST CSCs by looking for the occurrence of common CSC markers such as KIT, CD133, CD90, CD44, and CD34 in 18 surgical samples obtained from nine untreated and nine imatinib-treated KIT-mutated GIST patients. Results: The results indicated the homogeneous and previously unreported expression of CD133 (18/18), CD90 (15/16), and CD44 (12/14), together with KIT (18/18) and CD34 (13/18). This profile is similar to that identified in bone marrow mesenchymal progenitors and does not seem to be significantly modified by imatinib as only marginal changes in KIT and CD133 expression (P ≤0.05, Mann-Whitney test) were found in the treated samples. Conclusions: These findings suggest that GISTs are a clonal expansion of quite primitive cells that strictly depend on KIT oncogenic addiction, and have no cancer/stem cell component that can be detected by means of the antigens used in this study.

Original languageEnglish
Pages (from-to)238-247
Number of pages10
JournalCytometry Part B - Clinical Cytometry
Volume80 B
Issue number4
DOIs
Publication statusPublished - Jul 2011

Keywords

  • cancer stem cells
  • CD133
  • gastrointestinal stromal tumours
  • imatinib
  • KIT

ASJC Scopus subject areas

  • Cell Biology
  • Histology
  • Pathology and Forensic Medicine

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