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Soluble Fas in serum from patients with renal cell carcinoma
N Nonomura1, K Nishimura, Y Ono
1Department of Urology, Osaka University Medical School, Suita-city, Japan.
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.
Insights
Elevated soluble Fas (sFas) levels in renal cell carcinoma (RCC) patients may indicate an immune response to tumor burden, not the tumor itself. Post-surgery, sFas levels often decreased, suggesting its potential as a tumor burden indicator.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Fas/APO-1 is a key apoptosis receptor in the TNF receptor family.
- The Fas-Fas ligand system is crucial for immune responses against tumor cells.
- Soluble Fas (sFas) can antagonize cell-surface Fas interactions.
Purpose of the Study:
- To investigate serum sFas levels in renal cell carcinoma (RCC) patients.
- To explore the correlation between sFas levels and RCC clinicopathologic parameters.
Main Methods:
- Reverse transcriptase-polymerase chain reaction (RT-PCR) to detect sFas mRNA in RCC cell lines and tissues.
- Enzyme-linked immunosorbent assay (ELISA) to quantify serum sFas levels in 31 RCC patients before and after nephrectomy.
Main Results:
- sFas mRNA was detected in RCC cell lines and tissues.
- Serum sFas levels were significantly higher in RCC patients compared to controls.
- Serum sFas levels correlated with tumor size and decreased post-nephrectomy in most cases.
Conclusions:
- Elevated serum sFas in RCC patients likely reflects an immune response to tumor burden.
- Serum sFas may serve as a valuable biomarker for assessing tumor burden in RCC.
