Biology of glioblastomas and brain metastases and potential therapeutic targets


Giuliana Pelicci


Our lab is performing both basic and translational cancer research in the fields of brain tumors, brain metastases and cancer stem cells (CSCs). Our final goal is to identify and unravel the molecular mechanisms underlying glioblastoma (GBM) generation and progression. GBM is the most common and lethal type of glioma in adults. CSCs, able to generate and propagate the tumor and produce differentiated progeny with limited replicative potential, have been isolated in GBM and although the presence of surface markers selectively expressed on CSCs has been used to isolate these cells, no marker or pattern of markers is still sufficiently robust to definitively identify CSCs. In spite of the uncertainty and difficulties related to markers clearly identifying CSCs in GBM, it becomes essential to develop multiple strategies for CSC detection.

  • Research projects

    The aim of our research is to map CSC biomarkers from patient-derived tumor samples and to study proteins involved in GBM generation and progression.
    i) We recently demonstrated that RAI is a novel regulator of GBM invasion. RAI expression in cancer stem cells obtained from human GBM tumors allows their infiltration throughout brain parenchyma, preventing complete surgical resection and allowing relapse (Ortensi B. et al., 2012). Uncovering the molecular mechanisms regulating cancer infiltration would permit to set up new therapeutic strategies to block GBM invasion. We are now performing microRNA arrays to identify potential microRNAs involved in RAI regulation in CSCs, aiming at the identification of clinically relevant targets.
    ii) We recently demonstrated that CLIC1 (Chloride intracellular channel-1) is variably expressed in patient-derived GBM neurospheres and is enriched in the stem/progenitor compartment of the neurosphere (manuscript under review). Moreover, its silencing in GBM stem/progenitor cells negatively influences both proliferative capacity and self-renewal properties in vitro and impairs the in vivo tumorigenic potential. In addition to its role inside the tissue, CLIC1 has been identified as a secreted protein and detected in exosomes released from different cell types including glioma cells. Our goal is to elucidate the biological and clinical impact of CLIC1 secreted protein in glioblastoma.
    iii) A project currently ongoing in the lab aims at determining the CSC frequency in freshly dissociated human GBM samples, by means of in vitro and in vivo assays. This would fill an important gap in the knowledge of the brain tumor biology.
    iv) CSCs have been identified in different types of human cancer as the responsible of tumor initiation and propagation. In human GBM these cells have been isolated mostly on the basis of the expression of the cell surface protein CD133. We have recently demonstrated that the functional role of CD133 in the stem cell compartment is strictly related to its cell surface localization, giving a new insight in the biological function of this protein in GBM stem cells (Brescia et al., 2013). We are interested in the study of potential CSC markers that could be used in clinical applications.
    v) Brain metastases are the most common malignancy of the CNS. The knowledge of the biology regulating brain metastasis is fragmentary. The existence of metastasis-initiating cells has not yet been proved, although some evidences suggest that these cells might be found within subpopulations of CSCs. Our projects aim to i) identify specific molecular alterations in the brain metastases; ii) understand the mechanisms of organ-specific metastatic program: study of the relevance of the blood-brain barrier and/or the specific niche in brain metastases formation; iii) define the molecular subtypes that identify patients at high risk of developing brain metastases. To achieve these aims we will study brain metastases derived from breast tumors.

  • Publications

    • Setti M, Savalli N, Osti D, Richichi C, Angelini M, Brescia P, Fornasari L, Carro MS, Mazzanti M, Pelicci G. Functional Role of CLIC1 Ion Channel in Glioblastoma-Derived Stem/Progenitor Cells. J Natl Cancer Inst. 2013 Nov 6;105(21):1644-55.
    • Richichi C, Brescia P, Alberizzi V, Fornasari L, Pelicci G. Marker-independent method for isolating slow-dividing cancer stem cells in human glioblastoma, Neoplasia. 2013 Jul;15(7):840-7.
    • Brescia P, Ortensi B, Fornasari L, Levi D, Broggi G, Pelicci G. CD133 is essential for glioblastoma stem cell maintenance Stem Cells. 2013 May 31; (5):857-69.
    • Ortensi B, Setti M, Osti D, Pelicci G. Cancer stem cell contribution to glioblastoma invasiveness. Stem Cell Res Ther. 2013 Feb 28;4(1):18.
    • Ortensi B*, Osti D*, Pellegatta S, Pisati F, Brescia P, Fornasari L, Levi D, Gaetani P, Colombo P, Ferri A, Nicolis S, Finocchiaro G, Pelicci G. Rai is a new regulator of neural progenitor migration and glioblastoma invasion Stem Cells. 2012 May;30(5):817-32.


    All publications



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