Abstract
BackgroundMeningioma cancer stem cells (MCSCs) contribute to tumor aggressiveness and drug resistance. Successful therapies developed for inoperable, recurrent, or metastatic tumors must target these cells and restrict their contribution to tumor progression. Unfortunately, the identity of MCSCs remains elusive, and MSCSs’ in situ spatial distribution, heterogeneity, and relationship with tumor grade, remain unclear.MethodsSeven tumors classified as grade II or grade III, including one case of metastatic grade III, and eight grade I meningioma tumors, were analyzed for combinations of ten stem cell (SC)-related markers using immunofluorescence of consecutive sections. The correlation of expression for all markers were investigated. Three dimensional spatial distribution of markers were qualitatively analyzed using a grid, designed as a repository of information for positive staining. All statistical analyses were completed using Statistical Analysis Software Package.ResultsThe patterns of expression for SC-related markers were determined in the context of two dimensional distribution and cellular features. All markers could be detected in all tumors, however, Frizzled 9 and GFAP had differential expression in grade II/III compared with grade I meningioma tissues. Correlation analysis showed significant relationships between the expression of GFAP and CD133 as well as SSEA4 and Vimentin. Data from three dimensional analysis showed a complex distribution of SC markers, with increased gene hetero-expression being associated with grade II/III tumors. Sub regions that showed multiple co-staining of markers including CD133, Frizzled 9, GFAP, Vimentin, and SSEA4, but not necessarily the proliferation marker Ki67, were highly associated with grade II/III meningiomas.ConclusionThe distribution and level of expression of CSCs markers in meningiomas are variable and show hetero-expression patterns that have a complex spatial nature, particularly in grade II/III meningiomas. Thus, results strongly support the notion of heterogeneous populations of CSCs, even in grade I meningiomas, and call for the use of multiple markers for the accurate identification of individual CSC subgroups. Such identification will lead to practical clinical diagnostic protocols that can quantitate CSCs, predict tumor recurrence, assist in guiding treatment selection for inoperable tumors, and improve follow up of therapy.
Highlights
Meningioma cancer stem cells (MCSCs) contribute to tumor aggressiveness and drug resistance
Cells positive for nuclear SOX2 and cytoplasmic Frizzled 9 (FZD9) were consistently seen in niche-stained foci, while cells positive for cytoplasmic Vimentin were detected in large positive regions and had homo-expression patterns
Cells positive for Nestin, CD133, glial fibrillary acidic protein (GFAP), BIIIT, Stage-specific embryonic antigen-4 (SSEA4), and Olig2 had a tumordependent pattern of expression, which did not have a dichotomous association with grade
Summary
Meningioma cancer stem cells (MCSCs) contribute to tumor aggressiveness and drug resistance. Genetic analyses of bulk meningioma tissues identified mutations in several pathways including the phosphoinositide 3-kinase (PI3K) and the G protein-coupled receptor smoothened (SMO) signaling pathways [4,5,6]. These tumors are classified by the World Health Organization (WHO) into 15 variants within grades I to III. A range of genes and their proteins have been associated with the identity of CNST CSCs. CD133/Prominin-1, a five-transmembrane glycoprotein, is normally expressed in embryonic neural SC radial glial/ependymal cells and in ependymal cells in the adult brain [15]. Higher CD133 expression correlates positively with cell proliferation and drug resistance [9, 13, 22, 23]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
