0-TESTO COMPLETO.pdf - Fondazione Santa Lucia

Sezione III: Attività per progetti
LIST OF PARTICIPATING UNITS
U.O. 1 – IRCCS INM Neuromed, Pozzilli (Is) – Ferdinando Nicoletti
U.O. 2 – Università di Roma La Sapienza, Department of Human Physiology
and Pharmacology – Daniela Melchiorri
U.O. 3 – IRCCS Istituto Carlo Besta, Milano – Gaetano Finocchiaro
U.O. 4 – Università di Roma La Sapienza, Department of Experimental
Medicine – Antonella Calogero
U.O. 5 – Università di Catania, Department of Chemical Sciences –
Daniela Condorelli
U.O. 6 – IRCCS Fondazione Santa Lucia, Roma – Daniela Barilà
U.O. 7 – Università di Roma La Sapienza, Department of Experimental
Medicine – Alberto Giulino
DESCRIPTION OF THE PROJECT
What is already known on the subjet
Primary CNS tumors account for 1-1.5% of all cancer and about 2.2% of all
cancer-related deaths [reviewed by Reardon et al. 2006]. Glial tumors are about
42% of all primary brain cancers, and over 75% are malignant. Like other types
of cancer, brain cancer originates from a series of mutations that occur in a few
cells. The hierarchical model predicts that only a rare subset of cells actively support
tumor growth, with the remaining cells of the tumor being differentiating or
differentiated cells. These tumor-initialing cells are commonly defined as cancer
stem cells [reviewed by Vescovi et al. 2006; Sanai et al. 2005].
The cancer-stem-cell theory well explains the high rate of recurrence of
malignant gliomas. Stem-like cells can be isolated from malignant gliomas
and expanded in culture. Isolated glioma stem cells share a number of
fcahlres with type-B neural stem cells of the subventricular zone. These cells,
which sustain neurogenesis for an entire lifespan cycle approximately every
month and give rise to type-C transient amplifying cells. which in turn generate
type-A migrating neuroblasts [reviewed by Ming and Song 2005]. The
identity of the subventricular zone as a source of malignant gliomas is supported
by the evidence that exposure to oncogenic viruses or carcinogens
induces the formation of tumors in this area [reviewed by Sanati et al. 2005].
The hypothetical link between neural stem cells and glioma stem cells led to
the prediction that these two cell type are regulated by similar mechanisms,
and that these mechanisms can be targeted by novel anticancer drugs. Bone
morphogenetic proteins, which are soluble factors that normally induce neural
stem cells to differentiate into astrocytes, can also induce the differentiation
of glioma stem cells, weakening their tumor-forming ability [Piccirillo et
al. 2006]. The following evidence suggests that metabotropic glutamate
(mGlu) receptors fit into this scenario. mGlu receptors form a family of eight
subtypes, which, by definition, are all coupled to GTP-binding proteins.
754 2009