Synthesis and secretion of alpha 2-macroglobulin by human glioma established cell lines

Human alpha 2-macroglobulin (alpha 2M) is a high molecular weight plasma proteinase inhibitor exhibiting a broad specificity; in fact it is capable of binding endopeptidases from all known classes of proteases (Barret 1981). Two human glioma cell lines, namely an astrocytoma and a glioblastoma, were found to synthesize and secrete in the culture medium a protein which resembles the serum alpha 2M for immunological, biochemical and biological features. Using polyclonal antibodies to serum alpha 2M, an alpha 2M-like factor could be detected in the cytoplasm and in the culture medium of the tumor cells. Furthermore this factor accumulated in cytoplasmic granules if cells were incubated with monensin and its production was dramatically reduced following a treatment with cycloheximide. This protein behaved like the serum alpha 2M in immunoblotting analysis and exhibited the same antiproteolytic activity. Its role in human brain is unknown at present. Since interactions of proteinases and proteinase-inhibitors appear to influence the host-tumor immune response and to play a crucial role during the migration of metastasizing tumor cells, alpha 2M expression observed in these glioma cells could be involved in tumor cell proliferation and invasion.