Expression of the IL-6 family cytokines in human brain tumors

Abstract

In our RT-PCR screen for cytokine expression in human brain tumors we discovered increased levels of oncostatin M (OSM), ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF), all belonging to the interleukin-6 (IL-6) cytokine family, in most of the tumors. The expression of these cytokines in normal adult brain tissue was found to be very low or below detection limit. OSM expression was elevated in most of the tumors and immunohistochemistry analysis showed that the tumor cells contained OSM in their cytoplasm, suggesting they produce this factor. Overexpression of OSM has not previously been reported in primary human brain tumors. The IL-6 cytokine family acts through a common gp130 receptor subunit that activates the JAK/STAT signaling pathway and therefore they have been suggested to have overlapping effects. Tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase 1 (MMP-1) and MMP-3 and IL-6 have been reported to be regulated by OSM. IL-6 was low or absent in the tumors. TIMP-1, MMP-1 and MMP-3 was expressed in most tumors but with no strict correlation to OSM levels.