Deciphering the role of developmental signalling pathways in modulating Glioblastoma aggressiveness and phenotype.
Glioblastoma multiforme (GBM) is the highest grade glioma, characterized by a rapid growth rate and an extensive infiltration into the surrounding brain tissue. In this context, in the last years the research group focused their interest in unveiling the mechanisms by which GBM tumor microenvironment (i.e. hypoxia) influences the activation of many developmental pathways and how their modulation impacts GBM biology. In particular, their studies are being committed to dissect the interplay between the hypoxic GBM microenvironment and the β-catenin/TCFs complex in order to identify the key determinants of GBM cell aggressiveness and their resulting phenotype. Moreover, the research team is historically involved in the characterization of the effects exerted by peculiar morphogens such as BMPs in GBM tumors. In particular, they previously demonstrated that the treatment of GBM cells with BMP2 is sufficient to induce a dramatic differentiation of these cells and to sensitize them to therapies. In this context, they are currently investigating the role of BMP9 as a dual inhibitor of GBM cell stemness and their transdifferentiation into tumor-derived endothelial cells (TDECs) and collaborate with the Department of Industrial Engineering for the synthesis and characterization of BMP2-mimicking peptides for GBM treatment.
Characterization of Medulloblastoma Cancer Stem Cells and their impact on therapy response.
Medulloblastoma (MB) is the most common malignant brain tumor of childhood. Although survival has slowly increased in the past years, the prognosis of these patients remains unfavourable. In this context, the research on paediatric MB has been focused in the study of intracellular signaling pathways, commonly activated during embryonic cerebellar development, that are often deregulated in MB. In particular, the research team exploited the fundamental role of microenvironmental hypoxia in maintaining MB stem-like cells, considered to be responsible for treatment resistance and recurrence. Along this line, they recently characterized the Notch pathway and the PI3K/AKT/mTOR intracellular axis as leading intracellular signalings implicated in MDB cell proliferation, survival, growth, and protein synthesis. Their recent interest is particularly focused on characterizing the therapy-induced proteomic evolution of MB tumors during anti-cancer treatments by the set up of a reliable in vitro model of MB cancer cell selection/evolution under the cytotoxic pressure of conventional drug combinations, in which identify the major factors involved in sustaining therapy resistance and tumor relapse.
- Elena Rampazzo
- Elena Porcù
- Francesca Maule
Selected PubblicationsRampazzo, E., Dettin, M., Maule, F., Scabello, A., Calvanese, L., D'Auria, G., Falcigno, L., Porcu, E., Zamuner, A., Della Puppa, A., et al.. 2017. A synthetic BMP-2 mimicking peptide induces glioblastoma stem cell differentiation. Biochim Biophys Acta, 1861, 2282-2292
Rampazzo, E., Persano, L., Pistollato, F., Moro, E., Frasson, C., Porazzi, P., Della Puppa, A., Bresolin, S., Battilana, G., Indraccolo, S., et al.. 2013. Wnt activation promotes neuronal differentiation of glioblastoma. Cell Death Dis, 4, e500
Persano, L., Pistollato, F., Rampazzo, E., Della Puppa, A., Abbadi, S., Frasson, C., Volpin, F., Indraccolo, S., Scienza, R., and Basso, G.. 2012. BMP2 sensitizes glioblastoma stem-like cells to Temozolomide by affecting HIF-1alpha stability and MGMT expression. Cell Death Dis, 3, e412
Pistollato, F., Abbadi, S., Rampazzo, E., Persano, L., Della Puppa, A., Frasson, C., Sarto, E., Scienza, R., D'Avella, D., and Basso, G.. 2010. Intratumoral hypoxic gradient drives stem cells distribution and MGMT expression in glioblastoma.. Stem Cells, 28, 851-862.
Pistollato, F., Rampazzo, E., Persano, L., Abbadi, S., Frasson, C., Denaro, L., D'Avella, D., Panchision, D. M., Della Puppa, A., Scienza, R., and Basso, G.. 2010. Interaction of hypoxia-inducible factor-1alpha and Notch signaling regulates medulloblastoma precursor proliferation and fate.. Stem Cells, 28, 1918-1929.
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