Nonomura N, Nishimura K, Ono Y, Fukui T, Harada Y, Takaha N, Takahara S, Okuyama A
Department of Urology, Osaka University Medical School, Suita-city, Japan.
Urology. 2000 Jan;55(1):151-5. doi: 10.1016/s0090-4295(99)00379-9.
Fas/APO- 1 is an apoptosis-signaling cell-surface receptor belonging to the tumor necrosis factor receptor family. The Fas-Fas ligand system plays an important role in cytotoxic T-lymphocyte-mediated or natural killer cell-mediated cytotoxicity against tumor cells. Soluble Fas (sFas), generated by alternative splicing, has been reported to antagonize the interaction of cell-surface Fas with Fas ligand. This study examined the level of sFas in the serum of patients with renal cell carcinoma (RCC) and investigated the correlation between the sFas level and clinicopathologic parameters of RCC.
Using reverse transcriptase-polymerase chain reaction, we examined the production of sFas messenger RNA (mRNA) from the cultured human RCC cell lines ACHN and OUR-10 and from surgical specimens. We also measured sFas levels in the serum of 31 patients with RCC before and after nephrectomy using an sFas-specific enzyme-linked immunosorbent assay.
mRNA of sFas was identified both in cultured ACHN cells and human RCC tissues, although mRNA of wild-type Fas was exclusively predominant. The level of sFas in the serum of patients with RCC was significantly higher than that of normal controls, but sFas was not detectable in the supernatant of cultured renal cancer cells. Preoperative and postoperative serum sFas levels did not clearly correlate with the patients' age or sex or with histologic stage, grade, or cell type of RCC. The serum sFas level in patients with RCC correlated with tumor size. In 24 of the 31 cases, radical nephrectomy reduced the serum sFas level within 3 months.
Our results suggest that the elevated serum sFas level in patients with RCC might not be derived from the tumor itself but might reflect an immune response to the tumor burden. Serum sFas may be a useful indicator of tumor burden in patients with RCC.
Fas/APO-1是一种属于肿瘤坏死因子受体家族的凋亡信号细胞表面受体。Fas-Fas配体系统在细胞毒性T淋巴细胞介导或自然杀伤细胞介导的针对肿瘤细胞的细胞毒性中起重要作用。据报道，通过可变剪接产生的可溶性Fas（sFas）可拮抗细胞表面Fas与Fas配体的相互作用。本研究检测了肾细胞癌（RCC）患者血清中sFas的水平，并探讨了sFas水平与RCC临床病理参数之间的相关性。
我们使用逆转录聚合酶链反应检测了培养的人RCC细胞系ACHN和OUR-10以及手术标本中sFas信使核糖核酸（mRNA）的产生。我们还使用sFas特异性酶联免疫吸附测定法测量了31例RCC患者肾切除术前和术后血清中的sFas水平。
在培养的ACHN细胞和人RCC组织中均鉴定出sFas的mRNA，尽管野生型Fas的mRNA占主导地位。RCC患者血清中的sFas水平明显高于正常对照组，但在培养的肾癌细胞上清液中未检测到sFas。术前和术后血清sFas水平与患者的年龄、性别或RCC的组织学分期、分级或细胞类型均无明显相关性。RCC患者血清中的sFas水平与肿瘤大小相关。在31例患者中的24例中，根治性肾切除术在3个月内降低了血清sFas水平。
我们的结果表明，RCC患者血清中sFas水平升高可能并非源于肿瘤本身，而是可能反映了对肿瘤负荷的免疫反应。血清sFas可能是RCC患者肿瘤负荷的有用指标。
