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: Immunofluorescence experiments on human GBM samples were conducted to investigate the role of the HH pathway in mediating the interaction of ECs with GSCs. As shown in Figure 1, CD31+ ECs were located close to CD133+ GSCs (Figure 1A), which is in agreement with our previous study 12. These CD31+ ECs appeared to be immature microvessels that were diffuse and/or lined and not completely intact. Furthermore, most CD31+ ECs expressed and secreted Shh in human GBM samples, although some tumour cells were surrounded with Shh (Figure 1B), indicating that ECs were an important source of Shh. We then observed that in the primary samples, Shh was detected in the area close to CD133+ cells, indicating that CD133+ GSCs were located next to Shh-expressing cells or surrounded by Shh (Figure 1C). Further, we found that glioma cells closer to CD31+ ECs had a significantly higher expression of Gli1 in the nuclei (Figure 1D). After quantitatively analysing Gli1+ GBM cells and their correlations to ECs, we found that most of Gli1-expressed GBM cells were perivascular cells (pGCs; 65.99 ± 7.11%) and some were distant cells (dGCs; 34.00 ± 7.12%; see supplementary material, Figure S1A, B). Additionally, we confirmed that these CD31+ cells also expressed VE-cadherin (Figure 1E) but not CD45 (Figure 1F), indicating that they were not haematopoietic. Our data suggest that the HH pathway may participate in the interaction between GSCs and 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.