Peduto Eberl L, Guillou L, Saraga E, Schröter M, French L E, Tschopp J, Juillerat-Jeanneret L
Institute of Pathology, University of Lausanne, Switzerland.
Int J Cancer. 1999 May 31;81(5):772-8. doi: 10.1002/(sici)1097-0215(19990531)81:5<772::aid-ijc18>3.0.co;2-s.
CD95/APO-1 ligand (FasL) is implicated in the maintenance of immune privileged sites by inducing apoptosis of activated infiltrating T lymphocytes. Therefore, progressive tumors might express high levels of FasL and develop as immune privileged sites. In this study, we investigated the expression of FasL and CD95/APO-1 (Fas, the FasL-receptor) in vitro in rat adenocarcinoma cell lines and the localization in situ in normal human kidney and colon and in their adenocarcinomas. The rat cell line PROb (a progressive tumor in vivo) expressed a higher level of FasL than the sister cell line REGb (a regressive tumor in vivo), as detected by flow cytometry. The 2 cell lines expressed the same level of Fas, but were resistant to FasL-induced apoptosis. In human tissue, both kidney and colon extracts expressed FasL by Western blot. Further investigations, using immunohistochemical staining of paraffin sections, showed that normal colon mucosa expressed Fas and FasL in crypt epithelial cells in the subnuclear compartment. Normal kidney showed Fas and FasL labeling mostly restricted to epithelial cells of proximal tubules and Henlé's loop, showing that this expression is not uniform throughout the organ. Smooth-muscle cells of muscularis propria and blood vessels in and around the tumors were also intensely but more uniformly labeled. In colon-cancer cells, FasL expression remained strong, whereas Fas expression was significantly reduced. A similar reduction in Fas expression was noted in renal-cancer cells. Tumor-infiltrating immune cells of the macrophage lineage do not express FasL. Our results show that smooth-muscle cells of muscularis propria and blood vessels are able to express FasL and to a slight extent Fas. In normal epithelial cells of colon and kidney, Fas and FasL are often co-expressed. The reduced expression of Fas in corresponding cancer cells in combination with the ability to express FasL might facilitate immune escape.
CD95/APO-1配体（FasL）通过诱导活化的浸润性T淋巴细胞凋亡，参与免疫赦免部位的维持。因此，进展性肿瘤可能表达高水平的FasL，并发展为免疫赦免部位。在本研究中，我们调查了FasL和CD95/APO-1（Fas，FasL受体）在大鼠腺癌细胞系中的体外表达，以及在正常人类肾脏、结肠及其腺癌中的原位定位。通过流式细胞术检测，大鼠细胞系PROb（体内进展性肿瘤）比其姐妹细胞系REGb（体内退行性肿瘤）表达更高水平的FasL。这两种细胞系表达相同水平的Fas，但对FasL诱导的凋亡具有抗性。在人体组织中，肾脏和结肠提取物通过蛋白质印迹法均表达FasL。进一步使用石蜡切片免疫组织化学染色研究表明，正常结肠黏膜在核下区的隐窝上皮细胞中表达Fas和FasL。正常肾脏显示Fas和FasL标记大多局限于近端小管和髓袢的上皮细胞，表明这种表达在整个器官中并不均匀。肿瘤内及周围的固有肌层平滑肌细胞和血管也有强烈但更均匀的标记。在结肠癌细胞中，FasL表达仍然很强，而Fas表达显著降低。在肾癌细胞中也观察到类似的Fas表达降低。肿瘤浸润的巨噬细胞系免疫细胞不表达FasL。我们的结果表明，固有肌层平滑肌细胞和血管能够表达FasL，并且在一定程度上表达Fas。在结肠和肾脏的正常上皮细胞中，Fas和FasL常共同表达。相应癌细胞中Fas表达的降低与表达FasL的能力相结合，可能促进免疫逃逸。
