The TGF-β Family in Glioblastoma

Abstract

Members of the transforming growth factor β (TGF-β) family have been implicated in the biology of several cancers. In this review, we focus on the role of TGFβ and bone morphogenetic protein (BMP) signaling in glioblastoma. Glioblastoma (GBM) is the most common malignant brain tumor in adults; it presents at a median age of 64 years, but can occur at any age, including childhood. Unfortunately, there is no cure, and even patients undergoing current treatments (surgical resection, radiotherapy, and chemotherapy) have a median survival of 15 months. There is a great need to identify new therapeutic targets to improve the treatment of GBM patients. TGF-βs signaling promotes tumorigenesis in glioblastoma, while BMPs suppress tumorigenic potential by inducing tumor cell differentiation. In this review, we discuss the actions of TGF-βs and BMPs on cancer cells as well as in the tumor microenvironment, and their use in potential therapeutic intervention.

The Impact of A3AR Antagonism on the Differential Expression of Chemoresistance-Related Genes in Glioblastoma Stem-like Cells

“…One term addressed is the so-called "TGF-β paradox", which refers to the dual impact of TGF-β on cancer progression, as TGF-β can act as a potent tumor suppressor in early-stage tumors by inducing robust antiproliferative responses, cellular differentiation, and apoptosis [63]. However, in advanced-stage cancer, TGF-β has the potential to promote many of the malignant features of GB, such as migration/invasion, angiogenesis, immunosuppression, and drug resistance/radioresistance [63][64][65][66]. Specifically, in our analysis, we detected that high expression of TGFB1 in GB correlates with a poor prognosis.…”

Understanding the Role of Endothelial Cells in Glioblastoma: Mechanisms and Novel Treatments

“…In addition to playing a key role in embryonic development and cell differentiation, recent evidence suggests BMPs may also play a role in cancer progression [ 131 , 132 ]. Some state that BMPs induce tumor cell differentiation, thereby suppressing tumorigenic potential [ 133 ]. For instance, BMP 4 halts the cell cycle of glioma cells, thereby decreasing their proliferation [ 134 ].…”

“…BMP 2 inhibitors have been shown to decrease tumor growth both in vitro and in vivo in glioblastoma [ 132 ]. BMPs also increase glioblastoma invasiveness by promoting tumor cell migration [ 133 , 137 ]. BMP 9 triggers Smad 1, 5, 8 phosphorylation and induces cell cycle progression [ 138 ].…”