| Abstract: |
Background: Alpha interferon (IFN-α) is commonly used to treat patients with advanced renal cell carcinoma (RCC). We previously reported that resistance of RCCs to IFN-α in vitro correlated with the expression of a cell-surface glycoprotein of 160,00 kD molecular weight (gp160) which we subsequently identified as aminopeptidase A. Materials and methods: To directly test the role of gp160/APA in IFN-resistance, we stably introduced the gp160/APA cDNA into IFN-sensitive SK-RC-49 cells resulting in the expression of an enzymatically active gp160/APA protein. In addition, to determine if gp160/APA expression could function as a marker of IFN-resistance in vivo, we assessed gp160/APA protein levels in autologous normal kidney and primary renal cancer specimens from 29 patients half of which were randomized to receive adjuvant IFN-α therapy following nephrectomy. Results: Four clones which possessed varying amounts of gp160/APA specific enzyme activity were assayed for sensitivity to the antiproliferative effects of IFN-α. All four clones exhibited sensitivity to IFN-α similar to that observed with parental SK-RC-49 cells. The analysis of tumor tissue detected no significant difference between the mean level of gp160/APA in tissue from control and IFN-α treated patients (1.33 A.U. versus 0.9981 A.U., p = 0.23); however, the mean gp160/RPA level was significantly less in tumor tissue (mean = 1.15 A.U.) compared to normal tissue (mean = 2.15 A.U.; p < 0.00001). Within the IFN-α treated group, tumor gp160/APA levels did not correlate with the development of metastases or survival (p = 0.469). Conclusions: These data indicate that gp160/APA does not directly convey IFN-resistance to RCC cells and suggest that expression of gp160/APA in primary RCCs does not predict the benefit of IFN-α therapy. |
