High CD133 expression levels in gastrointestinal stromal tumors

Bozzi, Fabio; Conca, Elena; Manenti, Giacomo; Negri, Tiziana; Brich, Silvia; Gronchi, Alessandro; Tamborini, Elena; Pilotti, Silvana

doi:10.1002/cyto.b.20589

Cited by 10 publications

(10 citation statements)

References 36 publications

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“…However, the present findings, in agreement with the two recent studies (Arne et al, 2011; Bozzi et al, 2011), suggest that CD133 is universally expressed in GIST, compared to other sarcoma types. Among GIST clinical and molecular subsets, both CD133 and CD44 showed high transcriptional up-regulation in primary gastric tumors and in KIT mutants.…”

Section: Discussionsupporting

confidence: 93%

CD133 and CD44 are universally overexpressed in GIST and do not represent cancer stem cell markers

Guo

Zhang

Qin

et al. 2011

Genes Chromosomes & Cancer

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Although imatinib mesylate has been a major breakthrough in the treatment of advanced GIST, complete responses are rare and most patients eventually develop resistance to the drug. Thus the possibility of an imatinib-insensitive cell subpopulation within GIST tumors, harboring stem cell characteristics, may be responsible for the clinical failures. However, the existence of a cancer stem cell component in GIST has not been yet established. The present study was aimed to determine whether expression of commonly used stem cell markers in other malignancies, i.e. CD133 and CD44, might identify cells with characteristics of cancer stem/progenitor cells in human GIST. CD133 and CD44 expression in GIST explants was analyzed by flow cytometry, immunofluorescence, and gene expression. Their transcription levels were correlated with clinical and molecular factors in a large, well-annotated cohort of GIST patients. FACS sorted GIST cells based on CD133 and CD44 expression were isolated and used to assess phenotypic characteristics, ability to maintain their surface expression, sensitivity to imatinib, and expression signature. The enrichment in CD133/CD44 cells in the side population (SP) assay was also investigated. CD133 expression was consistently found in GIST. CD133− cells formed more colonies, were more invasive in a matrigel assay, and showed enrichment in the SP cells, compared to CD133+ cells. CD133 expression was also detected in the two imatinib-sensitive GIST cell lines, while was absent in the imatinib-resistant lines. Our results show that CD133 and CD44 are universally expressed in GIST, and may represent a lineage rather than a cancer stem cell marker.

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Section: Discussionsupporting

confidence: 93%

CD133 and CD44 are universally overexpressed in GIST and do not represent cancer stem cell markers

Guo

Zhang

Qin

et al. 2011

Genes Chromosomes & Cancer

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“…6 In line with a lineage marker rather than a CSCs marker, we found decreased CD133 expression in our imatinib-treated GISTs and no subpopulation of cells expressing high levels of CD133-and the same was true of KIT. 2 It is also worth noting that our findings are also in line with those of a recent study showing that the expression of CD133 in GIST is positively regulated by ETV1, a transcription factor that cooperates with KIT in GIST tumorigenesis, and is expected to be coexpressed with CD133 and KIT in all KIT-addicted GISTs. 7 Finally, in an elegant study of postnatal murine stomach, 8 Bardsley et al found that the interstitial cells of Cajal (ICC) progenitors (and ICC-derived GISTs) have low levels of KIT expression and do not depend on KIT signaling for their survival, and (in the light of the recently proposed ETV1 model) are, therefore, unable to stabilize ETV1 and induce CD133 transcription and expression.…”

Section: Dear Editorsupporting

confidence: 92%

“…The results of our own flow cytometry (FC) analysis of the expression of CD133 in naïve and imatinib-treated GISTs were partially different and led us to different conclusions. 2 Like Arne et al, we observed a trend toward higher CD133 expression in naïve GISTs carrying c-kit exon 11 mutations in aggregate in a gastric location than in those with an intestinal location but, because of the small number of c-kit deleted cases (n ¼ 4), we can neither confirm nor deny the association between high CD133 levels and the c-kit exon 11 deletions.…”

Section: Dear Editorcontrasting

confidence: 67%

The CD133 expression levels and its role as potential cancer stem cells marker in gastrointestinal stromal tumor

Bozzi

Tamborini

Pilotti

2012

Intl Journal of Cancer

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“…CD34 is a cell surface marker of hematopoietic stem cells [28], adipose derived stem cells [29] and cancer stem cells of skin cancer [30], colorectal adenocarcinoma [31], and gastrointestinal stromal tumours [32], [33]. CD34 expression is also primarily observed in mesenchymal tumours [34], [35].…”

Section: Resultsmentioning

confidence: 99%

Global Gene Expression Analysis of Canine Osteosarcoma Stem Cells Reveals a Novel Role for COX-2 in Tumour Initiation

et al. 2014

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Osteosarcoma is the most common primary bone tumour of both children and dogs. It is an aggressive tumour in both species with a rapid clinical course leading ultimately to metastasis. In dogs and children distant metastasis occurs in >80% of individuals treated by surgery alone. Both canine and human osteosarcoma has been shown to contain a sub-population of cancer stem cells (CSCs), which may drive tumour growth, recurrence and metastasis, suggesting that naturally occurring canine osteosarcoma could act as a preclinical model for the human disease. Here we report the successful isolation of CSCs from primary canine osteosarcoma, as well as established cell lines. We show that these cells can form tumourspheres, and demonstrate relative resistance to chemotherapy. We demonstrate similar results for the human osteosarcma cell lines, U2OS and SAOS2. Utilizing the Affymetrix canine microarray, we are able to definitively show that there are significant differences in global gene expression profiles of isolated osteosarcoma stem cells and the daughter adherent cells. We identified 13,221 significant differences (p = 0.05), and significantly, COX-2 was expressed 141-fold more in CSC spheres than daughter adherent cells. To study the role of COX-2 expression in CSCs we utilized the COX-2 inhibitors meloxicam and mavacoxib. We found that COX-2 inhibition had no effect on CSC growth, or resistance to chemotherapy. However inhibition of COX-2 in daughter cells prevented sphere formation, indicating a potential significant role for COX-2 in tumour initiation.

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High CD133 expression levels in gastrointestinal stromal tumors

Abstract: 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.

Cited by 10 publications

References 36 publications

CD133 and CD44 are universally overexpressed in GIST and do not represent cancer stem cell markers

CD133 and CD44 are universally overexpressed in GIST and do not represent cancer stem cell markers

The CD133 expression levels and its role as potential cancer stem cells marker in gastrointestinal stromal tumor

Global Gene Expression Analysis of Canine Osteosarcoma Stem Cells Reveals a Novel Role for COX-2 in Tumour Initiation

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