摘要
目的观察人横纹肌肉瘤(rhabdomyosarcoma,RMS)在体内、外拟态血管的形成能力;探讨angiopoietin-2(Ang2)和laminin5γ2(LN-5γ2)在肿瘤血管生成拟态(vasculogenic mimicry,VM)发生中的作用。方法应用三维培养技术、抗体阻断技术等观察人胚胎性横纹肌肉瘤细胞株RD细胞及小鼠黑色素瘤细胞株B16细胞在体外培养时拟态血管的形成能力并检测CD31、Ang2及LN-5γ2在VM形成过程中的表达改变。收集13例人横纹肌肉瘤石蜡包埋组织连续切片,观察拟态血管的存在,并应用免疫组织化学方法检测CD31、Ang2与LN-5γ2的表达。结果人胚胎性横纹肌肉瘤细胞RD三维培养后能够降解基质,形成空腔、裂隙样结构,在此过程中,LN-5γ2逐渐开始表达,而Ang2与CD31的表达出现不均衡增强,在血管腔样结构的管壁上Ang2、CD31与LN-5γ2均表达阳性。应用anti-Ang2及anti-LN-5γ2均能够抑制瘤细胞网环样结构的形成;anti-Ang2能降低LN-5γ2的表达强度。13例横纹肌肉瘤中VM形成率达69.2%。结论人横纹肌肉瘤在体内外都能够形成拟态血管。Ang2可能通过上调LN-5γ2的表达促进瘤细胞拟态血管的形成。
Purpose To investigate the capability of vasculogenic mimicry （VM） formation by rhabdomyosarcoma （RMS） ceils in vitro and vivo, and to approach the effect of angiopoietin-2 （Ang 2） and laminin5γ2 （LN-5γ2） on the VM signal transduction. Methods The VM emerging was observed in embryonal rhabdomyosarcoma cells （RD） and melanoma cells （B16） by three-dimensional cultures and antibody inhibition experiments, the expression change of CD31, Ang2 and LN-5γ2 in VM formation was detected by immunohistochemistry. The paraffin-embedded tissues of human rhabdomyosarcoma were collected, all cases were observed by serial sectioning, and the expression of Ang2, LN-5γ2 and CD31 was detected by immunohistochemistry. Results Human rhabdomyosarcoma cells （RD） degraded matrix and formed lumen structure, the expression of LN-5γ2 emerged, the Ang2 and CD31 unevenly enhanced in this process; the positive stain of LN-5γ2, Ang2 and CD31 deposited in the lumen wall that tumour cells formed finally. The antibody inhibition experiments showed anti-Ang2 could degrade the expression of LN-5γ2, and both of their antibodies could inhibit the formation of loop or networks. The exhibition rate of VM was 69. 2% in the 13 cases of rhabdomyosarcomas. Conclusions Human rhabdomyosarcoma can form VM in vitro and vivo. Ang2 can promote the formation of VM by mediating up-regulation of LN-5γ/2.
出处
《临床与实验病理学杂志》
CAS
CSCD
北大核心
2008年第6期721-724,共4页
Chinese Journal of Clinical and Experimental Pathology
基金
甘肃省中青年基金(3YS061-A25-032)
兰州大学医学基金(LZUYX200604)
