In situ characterization of stem cells-like biomarkers in meningiomas

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.Electronic supplementary materialThe online version of this article (10.1186/s12935-018-0571-6) contains supplementary material, which is available to authorized users.

Array expression meta-analysis of cancer stem cell genes identifies upregulation of PODXL especially in DCC low expression meningiomas

“…Previous work in meningiomas revealed different co-expression patterns of PROM1 and SOX2 in tissues compared to corresponding cell lines [12]. Whereas the average number of cells positive for both SOX2 and PROM1 significantly increased in GII + GIII meningioma cell lines, they significantly decreased in GII + GIII meningioma tissues compared to GI entities [10]. Taken together, these observations are compatible with a cyclic and microenvironmental-influenced expression of PROM1 [75, 76].…”

“…Furthermore, in non-muscle-invasive bladder cancer, lower expression of BRINP1 is associated with unfavorable prognosis [69]. PROM1 is a pentaspan transmembrane glycoprotein that has been described by different research groups as a CSC factor in meningiomas [9, 10, 12, 13]. In our survey, PROM1 was markedly downregulated in DCC low expression meningiomas in five array expression studies.…”

Characterization and comparison of genomic profiles between primary cancer cell lines and parent atypical meningioma tumors

“…We believe that the primary cell line established in our study is suitable for studies seeking to answer patient-specific research questions as well as for screening effective novel therapeutic agents. Further, we performed FACS analysis to analyze the expression of CD44 and CD133, which are known cancer stem cell (CSC) markers and have been proposed as candidate meningioma CSCs markers [46,47]. The atypical meningioma-derived cell line showed enhanced expression of CD44 in all the cells including CD133 + and CD133 − cell subpopulations.…”

Overlapping variants in the blood, tissues and cell lines for patients with intracranial meningiomas are predominant in stem cell-related genes

“…The clinical profiles for the patients and their tumours’ histopathological features are shown in Table S1. Haematoxylin and eosin representative sections of histological variants of meningiomas had been previously published [ 22 , 23 ].…”

“…The meningioma specimens were obtained within 30 min after the tumour removal, dissected into three portions, and processed for DNA/RNA extraction [ 20 ], tissue freezing at -80 °C [ 23 ], and cell culture initiation [ 22 ], according to previously published studies. Genomic DNA from the tumour and cell lines was extracted from an average of 30 mg of frozen tissue or 5×10 6 cells per cell line using All PrepDNA/RNA kits (Qiagen, Hilden, Germany) according to the manufacturer's instructions.…”