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CANCER STEM CELLS AND
ONCOLOGY RESEARCH
11th International Conference on
Journal of Medical Oncology and Therapeutics | Volume 3
N Baeza-Kallee et al., J Med Oncl Ther 2018, Volume 3
DECIPHERING THE ROLE OF A2B5 IN
GLIOBLASTOMAS
N Baeza-Kallee, E Denicolaï, A Tchoghandjian, C Colin, A El
Battari and D Figarella-Branger
Aix-Marseille University, France
Patterns of ganglioside expression are characteristic of a particular
cell type, tissue or tumour. This reflects their functional roles and
their involvement in biological functions such as adhesion, cell-cell
interaction and proliferation. In glioblastoma (GBM), not much has
been explored. Our interest ingliomagenesis led us to focus on A2B5, a
monoclonal antibody specific of polysialogangliosides and to a lesser
extend of polysialoproteins. Our previous results suggested that A2B5+
cells isolated from human GBM had properties of GBM cancer stem like
cells (CSLC) (1, 2, 3). To go further, it is now essential to establish the
relationship between gliomagenesis and A2B5 immunoreactivity. A2B5
IgM specifically recognizes trisialogangliosides from the c-series (mainly
GT3 and its acetylated form, but also GQ1c and GP1c) at the membrane.
As little is known about glycosyltransferases involved in ganglioside
biosynthesis, in a first step we focused on the ST8 alpha-N-acetyl-
neuraminide α-2,8-sialyltransferase 3 enzyme (ST8sia3), reported to add
a third sialic acid on GD3 by an α2-8 liaison to produce GT3. We developed
GBM cell lines with various levels of A2B5 reactivity by overexpressing/
suppressing ST8sia3 enzyme and tested for stem cell properties. To
achieve this goal, we introduced the ST8sia3 coding sequence into U87-
MG and U251-MG GBM cell lines which are not considered as GBM CSLC
but are highly proliferative and aggressivein vivo. Thus the overexpression
of ST8sia3 resulted in a huge increase of A2B5 immunoreactivity and
ST8sia3 and A2B5 were detected in the same cells by flow cytometry
and immunofluorescence. The increase of A2B5 immunoreactivity
induced deep changes in cell behavior. As compared to control cells,
the overexpression of ST8sia3 (thus increase of A2B5) triggered cellular
migration and proliferation but no difference in their clonogenic potential
was measured. Moreover, the survival of mice orthotopically injected
with ST8sia3+-overexpressing U87-MG cells was slightly reduced when
compared to mice injected with U87-MG control cell line. At this stage,
these results showed that A2B5 expression is positively correlated with a
more aggressive cellular behavior.
N Baeza-Kallee is currently working at the Aix
Marseille Université, INSERM, Marseille, France.
BIOGRAPHY