Aldehyde dehydrogenase and HSP90 co-localize in human glioblastoma biopsy cells

The concept of a stem cell subpopulation as understood from normal epithelial tissue or bone marrow function has been extended to our understanding of cancer tissue and is now the target of treatment efforts specifically directed to this subpopulation. In glioblastoma, as well as in other cancers, i...

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Bibliographic Details
Published in:Biochimie 2013-04, Vol.95 (4), p.782-786
Main Authors: Rappa, F., Cappello, F., Halatsch, M.-E., Scheuerle, A., Kast, R.E.
Format: Article
Language:English
Subjects:
Aldehyde dehydrogenase
Aldehyde Dehydrogenase - metabolism
Disulfiram
Gene Expression Regulation, Neoplastic
Glioblastoma
Glioblastoma - enzymology
Glioblastoma - metabolism
Glioblastoma - pathology
HSP90
HSP90 Heat-Shock Proteins - metabolism
Humans
Protein Transport
Ritonavir
Stem cell
Temozolomide
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Summary:The concept of a stem cell subpopulation as understood from normal epithelial tissue or bone marrow function has been extended to our understanding of cancer tissue and is now the target of treatment efforts specifically directed to this subpopulation. In glioblastoma, as well as in other cancers, increased expression of aldehyde dehydrogenase (ALDH) has been found localized within a minority sub-population of tumor cells which demonstrate stem cell properties. A separate body of research associated increased expression of heat-shock protein-90 (HSP90) with stem cell attributes. We present here results from our initial immunohistochemistry study of human glioblastoma biopsy tissue where both ALDH and HSP90 tended to be co-expressed in high amounts in the same minority of cells. Since 12% of all cells in the six biopsies studied were ALDH positive and 17% were HSP90 positive, by chance alone 2% would have been expected to be positive for both. In fact 7% of all cells simultaneously expressed both markers-a significant difference (p = 0.037). That two previously identified proteins associated with stem cell attributes tend to be co-expressed in the same individual glioblastoma cells might have clinical utility. Disulfiram, used to treat alcoholism for half-a century now, is a potent ALDH inhibitor and the old anti-viral drug ritonavir inhibits HSP90. These should be explored for the potential to retard aspects of glioblastoma stem cells' function subserved by ALDH and HSP90. ► Aldehyde dehydrogenase activity and expression of HSP90 are stem cell markers. ► In human glioblastoma biopsies 7% of cells express both markers. ► Several currently marketed drugs inhibit aldehyde dehydrogenase and HSP90.
ISSN:0300-9084
1638-6183
DOI:10.1016/j.biochi.2012.11.007