Cytokine, protease, and protease inhibitor secretion in meningioma primary cultures

Meningioma is the most common intracranial cancer and mostly benign, but 15–20% of cases are invasive WHO 2 and 3. The tumor tissue microenvironment is in part shaped by the multitude of secreted factors from both tumor and stromal cell compartments. Here we explored the secretome of primary meningioma cell cultures derived from meningioma WHO 1 and 2 with the use of antibody-based arrays, focusing on proteases, protease inhibitors, and cytokines. Meningioma cultures exhibited a consistent inflammatory secretome characterized by innate, pro-inflammatory chemokines and cytokines (IL-6, IL-8, MCP-1, MIP-1β) together with osteopontin (SPP1), angiogenin, and osteoprotegerin, in addition to lysosomal proteases Cathepsins (B, S, X/Z/P) and metalloproteinases MMP-2 and MMP-9 and their protease inhibitors TIMP-1 and − 2. By in vitro degradation assay we showed that macrophages degraded gelatin more efficiently than tumor cells; and demonstrated tumor cell surface-associated degradative activity in a WHO 2 meningioma. By multi-channel immunofluorescence IHC of four tissue samples from each WHO grade we found that SPP1 + macrophages constituted a minor, focalized subpopulation of tumor macrophages in WHO 1 (0.37% of total macrophage population), which expanded considerably to 21.4%% in WHO 3. In higher WHO grades, we also observed SPP1 deposition in ECM and expression in other cells than macrophages. CD44 isoforms were expressed by both immune cells and tumor cells. The 2D culture model retained expression of the core inflammatory signature of proteases and their inhibitors, cytokines, chemokines, and growth factors reported in literature for meningioma.