Formation of autocrine loops in human cerebral meningioma tissue by leukemia inhibitor factor, interleukin-6, and oncostatin M: inhibition of meningioma cell growth in vitro by recombinant oncostatin M.
It has been demonstrated that growth of cerebral meningiomas found in humans is controlled by a variety of factors, including growth factors, aminergic agents, neuropeptides, and steroids. To further our knowledge of this process, the authors investigated the presence and function of the cytokines leukemia inhibitory factor (LIF), interleukin-6 (IL-6), and oncostatin M (OSM) on meningioma cell proliferation. Active transcription of LIF, IL-6, and OSM, their related receptors (LIF-R, IL-6-R, and gp130), and the consecutive signal-transducing molecules (STAT 1, STAT 3, and STAT 5a) were analyzed in reverse transcriptase-polymerase chain reaction experiments. The presence of endogenous LIF, IL-6, and OSM proteins was demonstrated in the supernatant of cultured meningioma cells using the enzyme-linked immunosorbent assay and Western blot experiments, thus indicating an autocrine signaling pathway for all three cytokines. The biological function of all three cytokines was evaluated by studying their effects on meningioma cell growth. Recombinant LIF and IL-6 showed no significant growth modulating effects; however, recombinant OSM decreased meningioma cell growth by 66%. The antiproliferative potency of OSM was demonstrated by cell count experiments, the [3H]thymidine incorporation assay, and cell cycle analysis. These in vitro data support the concept that growth of meningioma cells may be modulated by cytokines, and they also indicate that recombinant OSM may be one future candidate for use in the adjuvant treatment of inoperable and recurrent meningiomas.