Exth-57. the igf-2 signaling pathway is a promising meningioma treatment target

Abstract Meningioma is the most common primary central nervous system tumor often causing serious complications while there is no effective medical treatment. We developed a tumor-derived primary culture model featuring tumor cells with retained PDG2S lineage marker as well as non-arachnoid cells mimicking the tumor cell microenvironment. We used this model to test the relevance of miRNA differentially expressed in meningioma tumor samples identified by small RNA sequencing. We found that in all meningiomas studied, there was activation of the IGF2/miR-483 locus with high expression of both miR-483-5p and IGF2. Inhibition of miR-483-5p reduced the growth of cultured meningioma cells, whereas a miR-483 mimic increased cell proliferation. Anti-IGF2 neutralizing antibodies reduced meningioma cell proliferation. Small molecule tyrosine kinase inhibitor blockade of the IGF2 receptor (IGF1R) resulted in rapid loss of viability of cultured meningioma tumor-derived cells. Autocrine IGF2 feed-back appears to be obligatory for meningioma tumor cell survival and growth. Inhibition of this circuit with IGF1R small molecule tyrosine kinase inhibitors or receptor-binding antibodies as well as anti-IGF2 neutralizing antibodies may have therapeutic potential for meningioma.