Interleukin‐6 and transforming growth factor‐β synergistically stimulate chondrosarcoma cell proliferation

Abstract

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‐β (TGF‐β) was identified as an essential serum component, since the mitogenic effect of sera was related to their TGF‐β content and neutralized by antibody to TGF‐β. Among a large panel of agents tested, TGF‐β was the only factor that stimulated proliferation in serum‐free media. The TGF‐β isoforms TGF‐β1 and TGF‐β2 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‐β 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‐β (0.01–0.1 ng/ml). This synergy was unique, since no other factor tested synergized with IL‐6 or TGF‐β. In examining potential mechanisms for this synergy it was found that TGF‐β increased IL‐6 receptor expression. In summary, these results identify IL‐6 as a new and TGF‐β as the most potent growth factor for chondrosarcoma cells and describe novel interactions between these factors in the regulation of cell growth.