Transforming Growth Factor Beta Family in the Pathogenesis of Meningiomas.

Abstract

Meningiomas account for 36% of primary brain tumors. The pathogenesis of these tumors is not completely established, hindering development of effective chemotherapy. Numerous studies have identified alterations in several growth factors and receptor kinases that regulate meningioma growth. These may be targets for new therapies. One of these, sometimes overlooked, is the transforming growth factor beta (TGF-β) family of proteins. Its receptors and signaling pathways play a critical role in development or progression of many forms of neoplasia. Evidence suggesting a potential role for TGF-β, bone morphogenetic protein, and their mediators is reviewed. TGF-β inhibition of growth in normal leptomeninges may be lost in neoplasia. Moreover, loss of TGF-β and bone morphogenetic protein signaling components and TGF-β type III receptor likely contribute to the development and/or progression of higher grade meningiomas. Accumulating evidence suggests that derangement of TGF-β family signaling contributes to development and progression of meningiomas. The TGF-β family may represent new targets for chemotherapy and could include inhibitors of kinases activated by TGF-β.