Soluble Fas in serum from patients with renal cell carcinoma

Abstract

Objectives. 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. Methods. 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. Results. 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. Conclusions. 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.