This trend of stage-by-stage increase of gCSCs in gliomas showed statistical significance by chi-square test linear-by-linear association. We prove that the rates of existence of gCSCs increase proportionally as the WHO grades of gliomas rise.

Cancer stem cells (CSCs) have been reported to be critical in the initiation, maintenance, and progression of cancers. The expression of stem cell markers, such as podoplanin (PDPN), CD133, and nestin, may have been correlated with malignant progression. However, the effects of CSCs and stem cell markers on clinical outcomes in cancer patients remain unclear. In this study, we assessed the prognostic roles of glioma CSCs (gCSCs) isolation and stem cell markers in patients with primary glioblastoma (pGBM). A cohort of 39 patients with pGBM was separated into two groups, those positive or negative for gCSCs, and the correlation between gCSC and patient survival was evaluated. We observed significantly different cumulative survival (P = 0.045) when comparing patients positive for gCSCs patients and negative for gCSC. Among the patients positive for gCSCs, we observed no significant differences in survival between those whose gCSCs were each positive or negative for PDPN, CD133, or nestin. This study strongly supports the prognostic value of gCSCs isolation on the survival of patients with pGBM.

The presence of glioma stromal mesenchymal stem‑like cells (GS-MSLCs) in tumors from glioma patients has been previously reported. The mechanisms through which these cells function as a part of the glioma microenvironment, however, remain incompletely understood. We investigated the biological effects of GS-MSLCs on glioma cancer stem cells (gCSCs), testing the hypothesis that GS-MSLCs alter the biological characteristics of gCSCs. GS-MSLCs and gCSCs were isolated from different glioblastoma (GBM) specimens obtained from patients. In in vitro experiments, gCSCs were cultured alone or co-cultured with GS-MSLCs, and gCSCs cell counts were compared between the two groups. In addition, two groups of orthotopic GBM xenografts in mice were created, one using gCSCs from the monoculture group and one using gCSCs isolated from the co-culture group, and tumor volume and survival were analyzed. Furthermore, in vivo proliferation, apoptosis and vessel formation were examined using immunohistochemical analyses. In vitro cell counts for gCSCs co-cultured with GS-MSLCs increased 3-fold compared to gCSCs cultured alone. In orthotopic xenograft experiments, mice injected with gCSCs isolated from the co-culture group had significantly larger tumor volume, measured on day 40 after injection, and their survival times were shorter. Immunohistochemical analysis showed increased tumor expression of CD31, indicative of enhanced microvessel formation in mice injected with gCSCs co-cultured with GS-MSLCs compared to mice injected with gCSCs cultured alone. However, proliferation (PCNA) and apoptosis (TUNEL) markers showed no significant difference between the two groups. In conclusion, GS-MSLCs may influence the biological properties of gCSCs, shifting them towards a more aggressive status; moreover, increased angiogenesis may be a critical component of this mechanism.

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