Functional role of enzyme LOXL3 in astrocytoma

Abstract

Astrocytomas are of astrocytic tumors involving cells of the central nervous system and are the most frequent among gliomas tumors (tumors associated with glial cells). In the United States they take up 34% of all morphologic subtypes of gliomas and Brazil are also the most common, affecting mainly men. The World Health Organization classifies astrocytomas according to their malignancy, with grade I or pilocytic astrocytoma (PA), low-grade and grade IV, or glioblastoma (GBM), the most evil and the worst prognosis. Our laboratory compared the genes overexpression in GBM compared to AP, in order to identify new therapeutic targets. The enzyme gene lysyl oxidase (LOX) was found in one of overexpression in GBM. The enzyme LOX belongs to a family with five members (LOX, LOXL1, LOXL2, LOXL3 and LOXL4) and operates in catalysing crosslinks in collagen and elastin. Among the members of the LOX family, LOXL3 enzyme was the only one that had an impact on the prognosis of GBM cases: patients with overexpression of LOXL3 have a lower average survival compared to those with the gene in low level expression. LOXL3 has been identified as a possible contributor to cell migration and metastasis, through their involvement with the gene responsible for regulating epithelial-mesenchymal transition, Snail. This present study aims to investigate the functional role of LOXL3 as a potential therapeutic target in the treatment of GBM.