Emerging evidence has demonstrated transdifferentiation process of glioma stem cells (GSCs) into endothelial cells (ECs) in glioma neovascularization. Herein, we focused on screening for genes that were differentially expressed in the transdifferentiation process using microarray analysis. Bioinformatics analysis revealed differential expression of the prolyl 4-hydroxylase subunit alpha-1 (P4HA1) gene. We determined that P4HA1 expression was correlated with histological grade, the level of Ki67 and microvessel density (MVD) in human glioma specimens. Knockdown of P4HA1 inhibited the proliferation, migration and tube formation of GSCs in vitro. In vivo studies revealed that the downregulation of P4HA1 inhibited intracranial tumor growth, prolonged the overall survival time of xenograft mice and suppressed the neovascularization in brain tumors. Moreover, P4HA1 regulates the expression of vascular endothelial growth factor A (VEGF-A), especially an anti-angiogenic isoform-VEGF165b. Additionally, knockdown of P4HA1 inhibited the synthesis of collagen IV, and hence disrupted the structures of vascular basement membranes (BMs) in gliomas. Our study indicates that P4HA1 plays a pivotal role in the process of GSC-EC transdifferentiation and the structural formation of vascular BMs.
Our results suggest that FASN plays a pivotal role in glioma neovascularization, and inhibition of FASN may be a potential target for anti-angiogenic therapy for glioma.
Viruses have demonstrated strong potential for the therapeutic targeting of glioblastoma stem cells (GSCs). In this study, the use of a herpes simplex virus carrying endostatin–angiostatin (VAE) as a novel therapeutic targeting strategy for glioblastoma-derived cancer stem cells was investigated. We isolated six stable GSC-enriched cultures from 36 human glioblastoma specimens and selected one of the stable GSCs lines for establishing GSC-carrying orthotopic nude mouse models. The following results were obtained: (a) VAE rapidly proliferated in GSCs and expressed endo–angio in vitro and in vivo 48 h and 10 d after infection, respectively; (b) compared with the control gliomas treated with rHSV or Endostar, the subcutaneous gliomas derived from the GSCs showed a significant reduction in microvessel density after VAE treatment; (c) compared with the control, a significant improvement was observed in the length of the survival of mice with intracranial and subcutaneous gliomas treated with VAE; (d) MRI analysis showed that the tumor volumes of the intracranial gliomas generated by GSCs remarkably decreased after 10 d of VAE treatment compared with the controls. In conclusion, VAE demonstrated oncolytic therapeutic efficacy in animal models of human GSCs and expressed an endostatin–angiostatin fusion gene, which enhanced antitumor efficacy most likely by restricting tumor microvasculature development.
Collision tumors of the sellar region are relatively uncommon and consist mainly of more than one type of pituitary adenoma or a cyst or cystic tumor. The association of a pituitary adenoma and a craniopharyngioma is particularly rare. This study describes a rare occurrence in which a pituitary adenoma and a craniopharyngioma coexisted in the sellar region. The case involves a 47-year-old woman who underwent transsphenoidal surgery with subtotal tumor resection and reoperation using an interhemispheric transcallosal approach for total microsurgical resection of the tumor because the visual acuity in her left eye had re-deteriorated. Histopathological and immunohistochemical examinations of the excised tissue revealed a pituitary adenoma in the first operation and a craniopharyngioma in the second operation. Retrospective analysis found the coexistence of a pituitary adenoma and a craniopharyngioma, known as a collision tumor. Instead of the transsphenoidal approach, a craniotomy should be performed, to explore the suprasellar region.
We developed a highly efficient cell fusion method that can be applied in many fields, particularly cancer research. Our study has proven that tumor-tumor cell fusion hybrids in melanoma can acquire enhanced and specific metastatic potential. Thus, blockage of cell fusion may be a new strategy for melanoma metastasis therapy.
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