Integrins in glioblastoma: Still an attractive target?

Integrin-mediated signaling pathways have been found to promote the invasiveness and survival of glioma cells by modifying the brain microenvironment to support the formation of the tumoral niche. A variety of cells in the niche express integrin receptors, including tumor-associated macrophages, fibroblasts, endothelial cells and pericytes. In particular, RGD-binding integrins have been demonstrated to have an important role in the epithelial-mesenchymal transition process, considered the first step in the infiltration of tissue by cancer cells and molecular markers of which have been found in glioma cells. In simultaneous research, Small Molecule Integrin Antagonists (SMIA) yielded initially promising results in in vitro and in vivo studies, leading to clinical trials to test their safety and efficacy in combination with other anticancer drugs in the treatment of several tumor types. The initially high expectations, especially because of their antiangiogenic activity, which appeared to be a winning strategy against GBM, were not confirmed and this cast serious doubts on the real benefits to be gained from the use of SMIA for the treatment of cancer in humans. In this review, we provide an overview of recent findings concerning the functional roles of integrins, especially RGD-binding integrins, in the processes related to glioma cells survival and brain tissue infiltration. These findings disclose a new scenario in which recently developed SMIA might become useful tools to hinder glioblastoma cell dissemination.