Interferon-gamma interrupts autocrine growth mediated by endogenous interleukin-6 in renal-cell carcinoma.
Cells of the renal-cell carcinoma line ACHN constitutively produce IL-6, express the IL-6 receptor and use IL-6 in an autocrine fashion to augment their growth. Growth arrest of ACHN cells can be achieved by exposure of cells to neutralizing monoclonal antibody (MAb) to recombinant human (rh) IL-6. Treatment of ACHN cells with rh IFN-gamma also leads to inhibition of proliferation of these cells in a dose-dependent manner, that can be reversed by exogenous rh IL-6, while IFN-alpha, IL-2, IL-4 and vinblastine or 17-beta-estradiol has no effect on growth (3H-thymidine uptake) of ACHN cells and IL-6 expression. Studies on the mechanism of action of IFN-gamma revealed that IFN-gamma was acting by inhibiting the autocrine IL-6-mediated loop generated by ACHN.
Department of Internal Medicine I, University of Freiburg, Germany.
H J
HJ
Gruss
M A
MA
Brach
R H
RH
Mertelsmann
F
F
Herrmann
D002292:Carcinoma, Renal Cell / Q000473:pathology*; D002455:Cell Division; D007371:Interferon-gamma / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000235:genetics; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D007371:Interferon-gamma