| dc.description.abstract | Glioma is a fatal disease characterized by uncontrolled cellular proliferation and it is
the most common primary brain malignancy in adults. Despite years of research,
malignant glioma remains one of the most aggressive cancer, with an average
expectancy of life of 12-15 months after resection, radiotherapy and chemotherapy.
N6-isopentenyladenosine (iPA) is a modified nucleoside with a pentaatomic
isopentenyl moiety, derived from mevalonate, that induces inhibition of cell
proliferation in several tumor cell lines. It has been shown that iPA modulates the
expression of several proteins involved in the promotion of tumor growth, but only
recently, our studies suggested bone morphogenetic protein 4 (BMP4), part of the
transforming growth factor beta superfamily, as potential iPA target. According to
preliminary results, infact, iPA, in several human colorectal cancer and glioma cell
lines, is able to inhibit cell proliferation and to modulate, in a tumor specific way, the
expression of BMP4, involved in the migration, invasion and differentiation of tumor
cells.
SR141716 is an antagonist of cannabinoids receptor type 1 (CB1), involved in the
regulation of cellular processes linked to survival, proliferation, invasion and
angiogenesis in physiopathological conditions.
Our group showed that a majority of human glioma cell lines overexpresses CB1,
compared to normal human astrocytes, and that, in this cancer model, SR141716 is
able to induce apopstosis via G1 phase stasis. This study demonstrates also that
SR141716 increases the functional and selective expression of MICA/B on the
surface of malignant glioma cells through a mechanism that involves STAT3
inhibition. This makes SR141716 treated-glioma cells, a potent target for allogeneic
NK cell-mediated recognition through a NKG2D restricted mechanism. Although
further studies will be necessary to investigate the mechanism of action of these
molecules, these results shed new light on the oncogenic networks in the complex
biology of glioma. [edited by author] | it_IT |
