Abstract
Interleukin‐6 (IL‐6) is produced at high levels by renal cell carcinoma cell lines. The molecular mechanisms involved in its possible role as an autocrine growth factor were investigated. IL‐6 and IL‐6 receptor expression was investigated in 8 renal cell carcinoma (RCC) cell lines. The modulation of RCC cell line proliferation by an anti‐IL‐6 Ab, an IL‐6 antisense oligonucleotide (ASON) directed against the second exon of IL‐6 and cytokines inhibiting IL‐6 production (IL‐4 and IL‐13) was investigated. All 8 RCC cell lines expressed IL‐6 mRNA, produced IL‐6 and expressed the soluble and membrane‐bound gp130 chain of IL‐6 receptor. The gp80 chain of IL‐6 receptor was undetectable at the surface of the 8 RCC cell lines tested, while the soluble form of gp80 was detectable in the supernatant of one of these cell lines. The addition of a blocking IL‐6 Ab did not inhibit the proliferation of any of the 8 RCC cell lines. In contrast, IL‐6 ASON inhibited specifically IL‐6 production and the proliferation of all RCC cell lines. Exogenous IL‐6 failed to restore RCC cell line proliferation blocked by ASON, indicating that IL‐6 acts through an intracrine loop in RCC cell lines. IL‐13 and IL‐4 inhibited the proliferation of 7 of the 8 cell lines without interfering with IL‐6 or IL‐6 receptor expression. IL‐6 ASON inhibited the proliferation of the 8 RCC cell lines tested additively with IL‐4 or IL‐13. IL‐6 is an intracrine growth factor in renal cell carcinoma cell lines. © 2004 Wiley‐Liss, Inc.