Expression of FasL in squamous cell carcinomas of the cervix and cervical intraepithelial neoplasia and its role in tumor escape mechanism
Expression of FasL in squamous cell carcinomas of the cervix and cervical intraepithelial neoplasia and its role in tumor escape mechanism
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DOI：
10.1002/cncr.21697
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发表时间：
2006-03-01
期刊：
影响因子：
6.2
通讯作者：
Khleif, SN
中科院分区：
文献类型：
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作者：
Ibrahim, R;Frederickson, H;Khleif, SN
背景迄今为止，已经描述了恶性细胞逃离免疫系统的几种机制。其中之一是通过表达FasL。作者假设Fas/FasL相互作用使宫颈癌细胞能够诱导免疫系统细胞凋亡，从而逃避它们。作者检测了FASL在宫颈癌组织表面的表达。接下来，他们用抗人类白细胞共同抗原和TUNEL对相同的宫颈组织进行染色，以识别凋亡细胞。然后进行所有体外功能测定以测试宫颈癌细胞系表面表达的FASL是否负责诱导T细胞凋亡。最后，他们比较了FASL在正常和不典型增生宫颈组织中的表达。作者检测的宫颈癌组织中有94%表达FasL，标本中大多数凋亡细胞是白细胞，很少有肿瘤细胞。在体外功能测定中，仅表达Fas 1的细胞系而非Fas 1阴性细胞系能够诱导表达Fas的Jurkat细胞的凋亡。在检查正常宫颈组织时，作者发现FasL的表达仅限于基底细胞层，在基底上层观察到表达缺失，这使其成为免疫特权部位。相反，在宫颈不典型增生和鳞状细胞癌的不典型增生层中，Fast持续表达。目前研究的结果支持作者的假设，即Fast的持续表达在宫颈癌细胞逃避免疫系统的能力中起作用。
BACKGROUND. To date, several mechanisms have been described by which malignant cells escape from the immune system. One of these is through the expression of FasL. The authors hypothesized that the Fas/FasL interaction enables cervical carcinoma cells to induce apoptosis of the cells of the immune system and thereby escape from them.METHODS. The authors tested the expression of FASL on the Surface of cervical carcinoma tissues. Next, they stained the same cervical tissues with anti-human leukocyte common antigen and TUNEL to identify, apoptotic cells. All in vitro functional assay was then done to test if the FASL expressed oil the surface of cervical carcinoma cell lines was or was not responsible for inducing apoptosis in T-cells. Finally, they compared the expression of FASL on normal and dysplastic cervical tissues.RESULTS. Ninety-four percent of the cervical carcinoma tissues the authors tested expressed FasL and the majority of the apoptotic cells in the specimens were leukocytes with very few tumor cells. In the in vitro functional assay, only the Fasl expressing cell line and not the Fasl negative cell line was able to induce apoptosis of the Fas-expressing Jurkat cells. On examining the normal cervical tissues, the authors found that the expression of Fasl was confined to the basal cell layer with loss of expression observed in the suprabasal layers, which made it an immune privileged site. Conversely, there was persistent expression of Fast, in the dysplastic layers in cervical dysplasia and squamous cell carcinoma specimens.CONCLUSIONS. The findings of the current study support the authors' hypothesis that persistent expression of Fast, plays a role in the ability of cervical carcinoma cells to escape from the immune system.