Endothelial cells promote stem-like phenotype of glioma cells through activating the Hedgehog pathway.
Bottom Line: Microenvironmental regulation of cancer stem cells (CSCs) strongly influences the onset and spread of cancer.We observed that CD133(+) GSCs were located closely to Shh(+) endothelial cells in specimens of human glioblastoma multiforme (GBM).Knockdown of Smo in glioma cells led to a significant reduction of their CSC-like phenotype formation in vitro and in vivo.
Affiliation: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, Third Military Medical University and Key Laboratory of Tumour Immunopathology, Ministry of Education of China, Chongqing, 400038, People's Republic of China.Show MeSH
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Mentions: CD34+ ECs, arranged in linear fashion, clustered and in microvessels, were observed in glioma specimens. Gli1 expression was much stronger in glioma cells near ECs (see supplementary material, Figure S4). The expressions of Shh on ECs and Gli1 on pGCs were 72% (24/33) and 61% (20/33), respectively, in low-grade glioma (WHO grade II). In high-grade glioma (WHO grades III–IV), the positive rates of Shh on ECs and Gli1 on pGCs were 81% (26/32) and 84% (27/32), respectively. Higher expression of Shh on ECs was observed in 18% (6/33) of low-grade glioma and 44% (14/32) of high-grade glioma, while the higher expression of Gli1 on pGCs was 24% (8/33) in low-grade glioma and 47% (15/32) in high-grade glioma. Expressions of both Shh and Gli1 were significantly related to WHO grades of glioma but not to gender, age, KPS and tumour location (Table 1). Based on Shh/Gli1 expression, patients were divided into two groups, a negative or moderate group and a high-expression group. Kaplan–Meier analysis revealed that expressions of Shh on ECs (Figure 7A) and Gli1 on pGCs (Figure 7B) were all related to the length of patient survival, with high expression implying worse prognosis. Taken together, our results indicate that Shh on ECs and Gli1 on pGCs may be useful indicators of prognosis in glioma patients.
Affiliation: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, Third Military Medical University and Key Laboratory of Tumour Immunopathology, Ministry of Education of China, Chongqing, 400038, People's Republic of China.