FORMATION OF AUTOCRINE LOOPS IN HUMAN CEREBRAL MENINGIOMA TISSUE BY LEUKEMIA INHIBITOR FACTOR, INTERLEUKIN-6, AND ONCOSTATIN-M - INHIBITIONOF MENINGIOMA CELL-GROWTH IN-VITRO BY RECOMBINANT ONCOSTATIN-M

Object. It has been demonstrated that growth of cerebral meningiomas f ound in humans is controlled by a variety of factors, including growth factors, aminergic agents, neuropeptides, and steroids. To further ou r knowledge of this process, the authors investigated the presence and function of the cytokines leukemia inhibitory factor (LIF), interleuk in-6 (IL-6), and oncostatin M (OSM) on meningioma cell proliferation. Methods. Active transcription of LIF, IL-6, and OSM, their related rec eptors (LIF-R, IL-6-R, and gp130), and the consecutive signal-transduc ing molecules (STAT 1, STAT 3, and STAT 5a) were analyzed in reverse t ranscriptase-polymerase chain reaction experiments. The presence of en dogenous LIF, IL-6, and OSM proteins was demonstrated in the supernata nt of cultured meningioma cells using the enzyme-linked immunosorbent assay and Western blot experiments, thus indicating an autocrine signa ling pathway for all three cytokines. The biological function of all t hree cytokines was evaluated by studying their effects on meningioma c ell growth. Recombinant LIF and IL-6 showed no significant growth modu lating effects; however, recombinant OSM decreased meningioma cell gro wth by 66%. The antiproliferative potency of OSM was demonstrated by c ell count experiments, the [H-3]thymidine incorporation assay, and cel l cycle analysis. Conclusions. These in vitro data support the concept that growth of meningioma cells may be modulated by cytokines, and th ey also indicate that recombinant of inoperable and recurrent meningio mas.