The definition of the number and nature of the signal transduction pathways involved in the pathogenesis and the identification of the molecules promoting
metastasis spread might improve the knowledge of the natural history of
osteosarcoma, also allowing refine the prognosis and opening the way to novel therapeutic strategies. Phosphatydil
inositol (4,5) bisphosphate (PIP2), belonging to the
Phosphoinositide (PI) signal transduction pathway, was related to the regulation of
ezrin, an
ezrin-
radixin-
moesin protein involved in metastatic
osteosarcoma spread. The levels of PIP2 are regulated by means of the PI-specific
Phospholipase C (PLC)
enzymes. Recent literature data suggested that in
osteosarcoma the panel of expression of PLC
isoforms varies in a complex and unclear manner and is related to
ezrin, probably networking with
Ras GTPases, such as RhoA and Rac1. We analyzed the expression and the subcellular localization of PLC
enzymes in cultured human
osteosarcoma MG-63 cells, commonly used as an experimental model for human osteoblasts, using
U-73122 PLC inhibitor,
U-73343 inactive analogue, and by silencing
ezrin. The treatment with
U-73122 significantly reduces the number of MG-63 viable cells and contemporarily modifies the expression and the subcellular localization of selected PLC
isoforms.
U-73122 reduces the cell growth in cultured MG-63 ostesarcoma cell line involving PI-specific
Phospholipases C.