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: To determine whether HH pathway activation plays any role in glioma cells co-cultured with ECs, we examined the expression of Gli1 together with Hes1 and β-catenin, since they have all been reported as crucial to CSC self-renewal and proliferation 29–31. As shown in Figure 4A, Gli1 expression was significantly increased in GL261 cells co-cultured with ECs, but the expressions of both Hes1 and β-catenin remained unchanged. Meanwhile, increased Gli1 expression positively correlated with co-culture time (Figure 4A). Furthermore, Gli1 was over-expressed in the U251 cells co-cultured with HUVECs (Figure 4B). We then performed immunofluorescence confocal microscopic analysis to examine the translocation of Gli1, one of the critical indicators to demonstrate HH pathway activation. As shown in Figure 4C, Gli1 moved completely from the cytoplasm compartment to the nuclei in GL261 cells co-cultured with b.END3 cells, indicating that the HH pathway was functionally activated. However, the locations of both β-catenin and Hes1 were not affected by b.END3 cells (Figure 4C). Taken together, these results indicate that the HH pathway is activated in glioma cells when cultured with ECs.
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.