Interleukin-6 and transforming growth factor-beta synergistically stimulate chondrosarcoma cell proliferation.
This study examines the regulation of Swarm rat chondrosarcoma (SRC) cell proliferation in vitro. In serum-free cultures, SRC cells showed only transient DNA synthesis and this was increased by serum. Transforming growth factor-beta (TGF-beta) was identified as an essential serum component, since the mitogenic effect of sera was related to their TGF-beta content and neutralized by antibody to TGF-beta. Among a large panel of agents tested, TGF-beta was the only factor that stimulated proliferation in serum-free media. The TGF-beta isoforms TGF-beta 1 and TGF-beta 2 induced similar dose-dependent increases with maximal 62.5-fold stimulation at 10 ng/ml. Interleukin-6 (IL-6) was identified as a new factor that stimulated SRC proliferation. IL-6 effects were serum-dependent and their magnitude correlated with the TGF-beta content in different serum preparations. In serum-free cultures where IL-6 by itself had no detectable effect it caused up to 7.6-fold increased proliferation in the presence of small doses of TGF-beta (0.01-0.1 ng/ml). This synergy was unique, since no other factor tested synergized with IL-6 or TGF-beta. In examining potential mechanisms for this synergy it was found that TGF-beta increased IL-6 receptor expression. In summary, these results identify IL-6 as a new and TGF-beta as the most potent growth factor for chondrosarcoma cells and describe novel interactions between these factors in the regulation of cell growth.
Division de Rhumatologie, Hopital Cantonal, Geneva, Switzerland.
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Guerne
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Lotz
D000818:Animals; D001769:Blood; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002813:Chondrosarcoma / Q000378:metabolism / Q000473:pathology*; D003470:Culture Media; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004357:Drug Synergism; D006133:Growth Substances / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D051381:Rats; D011971:Receptors, Immunologic / Q000378:metabolism; D019947:Receptors, Interleukin-6; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D003470:Culture Media; D004273:DNA, Neoplasm; D006133:Growth Substances; D015850:Interleukin-6; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D016212:Transforming Growth Factor beta