Journal of Cell Science & Therapy
Open Access
ISSN: 2157-7013
+44 1300 500008
ISSN: 2157-7013
+44 1300 500008
Luca Persano
Accepted Abstracts: J Cell Sci Ther
Glioblastoma multiforme (GBM) is the most common malignant brain tumor, currently treated by surgical removal followed by radio- and Temozolomide (TMZ)-based chemotherapy. Although treatment strategies benefi t of continuous advances, outcome of GBM patients is still poor. Since the recent defi nition of GBM cancer stem cells, many researchers are focusing on unravelling the tissue environmental interactions involved in GBM stem cells regulation and maintenance. Aim of our group is the development of novel pro-diff erentiating treatment able to target the GBM stem-like cell population by itself or sensitize it to chemotherapy in order to induce GBM cell growth inhibition and eventually cell death. In this context we and others recently described the role of BMPs in promoting GBM cell diff erentiation. Our data show that BMP2, by inhibiting HIF-1α signalling, is able to sensitize GBM stem-like cells to Temozolomide (TMZ)-based chemotherapy and that BMP2/TMZ combined treatment induce strong diff erentiation and apoptosis of GBM cells resistant to standard therapies. Unfortunately it has been reported that 20% of GBM displayed epigenetic silencing of BMPR1B due to CpG methylation in its promoter region. Since this patients should not be aff ected by BMP2 pro-diff erentiating eff ects, we analyzed eff ects mediated by Wnt signalling activation in GBM cells. We found that Wnt pathway activation exerted a strong pro-neuronal diff erentiation of GBM stem-like cells and that this pro-diff erentiating eff ect involved a direct induction of Wnt-regulated pro-neuronal genes and a concomitant Notch signalling inhibition. In conclusion our data propose two distinct tools to induce strong diff erentiation of GBM derived stem cells and to eff ectively target them. Moreover we point to BMP and Wnt signalling activators as promising therapeutic strategies for future GBM management.
Luca Persano completed his Ph.D in Oncology and Surgical Oncology at the University of Padova in 2008. Since 2004 his research was focused on tumor microenvironment and angiogenesis. He now holds a post- doctoral position on the topic of brain tumor stem cells and their regulation by tumor environmental factors at the University of Padova, Department of Paediatrics headed by Prof. Giuseppe Basso. He has published more than 15 papers in peer-reviewed journals