engleski

Tracing neuroplastin in glioblastoma

Astrocytoma are the most common type of brain tumors. Glioblastoma, also known as grade IV astrocytoma, account for the most frequent malignant brain tumors which are known to develop rapidly and invade neighbouring brain tissue. The poor 5-year survival rate of patients marks glioblastoma as an almost invariably fatal disease. Still, due to its heterogeneity, the etiology of glioblastoma remains unknown. With its high resistance to variety of therapies, there is an urgent need for new molecular targets which would be used in precise treatments. It is known that one of the mechanisms of glioblastoma invasion are cell-cell interactions. One of the most prominent cell adhesion glycoproteins in brain tissue is neuroplastin (Np) which is involved in synaptic plasticity, but also related to regulation of calcium homeostasis as an auxiliary subunit of plasma membrane Ca2+-ATPase (PMCA). Neuroplastin was also found to promote tumour invasion in metastatic breast tumors. In this work we used Western blotting in order to investigate the expression of neuroplastin and PMCA4 in different types of astrocytoma, with emphasis on glioblastoma samples. The results were compared with those from healthy brain tissue. Our preliminary results of astrocytoma tissue and control tissue (n=29 and 5) showed that neuroplastin signal intensity is greatly decreased in tumors (p<2.3x10-9). PMCA4 signal intensity correlated with low neuroplastin signal (p<0.01). Interestingly, in calcified tumor tissue we observed no neuroplastin signal but PMCA4 signal intensity ranged from no signal (p<0.0001) to greater than in control tissue (p<0.0002). This certain heterogeneity concerning PMCA4 is probably due to calcification process progression. Our results suggest that Np-PMCA4 axis of calcium homeostasis maintenance is severely disturbed in astrocytoma tumors, especially glioblastoma, and could be a new target for therapy.

astrocytoma ; glioblastoma ; neuroplastin ; PMCA4

nije evidentirano