Abstract
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.
Highlights
Osteosarcoma comprises less than 1 % of cancers in the United States, occurring in less than 1000 patients per year
The present results confirm our previous observations in human osteosarcoma cell lines suggesting that each cell line owns a specific Phospholipase C (PLC) panel of expression and that a complex organization of PLC enzymes occurs
Our present results indicate that adding of U-73122 to the MG-63 cultures can significantly reduce the number of viable cells, slowing the growth within 24 h intervals
Summary
Osteosarcoma comprises less than 1 % of cancers in the United States, occurring in less than 1000 patients per year. It is the most common primary bone tumour in childhood and adolescence (Mirabello et al 2009a, b). The presence of metastasis confers worse prognosis for osteosarcoma affected patients (Meyers et al 2005). Metastasizing tumours partially respond to current therapies and represent the primary cause of cancer related mortality (Meyers et al 2005). Osteosarcoma includes several pathological entities, comprising of different clinical, radiological, and histological features (Mirabello et al 2009a, b; Gatta et al 2005). Osteosarcoma arises from a mesenchymal cell that owns or can acquire the ability to
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
