IL-6 as an intracrine growth factor for renal carcinoma cell lines.
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.
Alberti
Laurent
L
Equipe Cytokine et Cancer, Unité INSERM 590, Lyon, France.
Thomachot
Marie Cécile
MC
Bachelot
Thomas
T
Menetrier-Caux
Christine
C
Puisieux
Isabelle
I
Blay
Jean Yves
JY
D002292:Carcinoma, Renal Cell / Q000503:physiopathology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000503:physiopathology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis* / Q000502:physiology; D014407:Tumor Cells, Cultured
D007377:Interleukin-3; D015850:Interleukin-6; D016376:Oligonucleotides, Antisense; D019947:Receptors, Interleukin-6; D015847:Interleukin-4