Department of Surgery, St Jude Children's Research Hospital, University of Tennessee Health Science Center, Memphis, TN 38105-3678, USA.
Anticancer Res. 2010 Sep;30(9):3301-8.
The vascular niche necessary for cancer stem cell maintenance is a potential target for cancer therapy.
Human glioma xenografts were treated with IFN-β delivered systemically via a liver-targeted, adeno-associated viral vector. The vascular niche was examined with immunofluorescence for glioma stem cells, endothelial cells, and perivascular cells.
Although IFN-β was not directly toxic to glioma stem cells in vitro, IFN-β decreased tumor size and the number of stem cells recovered in both heterotopic and orthotopic models. Treatment with IFN-β increased perivascular cells investing the tumor vasculature (6-fold) distancing stem cells from endothelial cells. Additionally, vascular smooth muscle cells co-cultured between stem cells and endothelial cells decreased stem cell recovery.
Continuous delivery of IFN-β decreased the number of stem cells in glioma xenografts by disrupting the vascular niche through an increase in perivascular cells, which created a barrier between the glioma stem cells and the endothelial cells.
维持癌症干细胞所需的血管生态位是癌症治疗的潜在靶点。
通过肝靶向的腺相关病毒载体将 IFN-β 全身递送至人胶质瘤异种移植物中。通过免疫荧光检测胶质瘤干细胞、内皮细胞和血管周细胞的血管生态位。
尽管 IFN-β 在体外对胶质瘤干细胞没有直接毒性，但 IFN-β 减少了异质和原位模型中肿瘤大小和回收的干细胞数量。IFN-β 治疗增加了投资肿瘤血管的血管周细胞（6 倍），使干细胞与内皮细胞分离。此外，与内皮细胞共培养的血管平滑肌细胞减少了干细胞的恢复。
通过增加血管周细胞破坏血管生态位，连续递送 IFN-β 减少了胶质瘤异种移植物中的干细胞数量，从而在胶质瘤干细胞和内皮细胞之间形成了屏障。
