Gliomas are recurrent primary brain tumors classified according its proliferation rate and invasiveness. A preliminary study of gene expression in material obtained from patients with glioma showed a significant negative correlation between the grade of invasiveness and the expression of the gene that encodes the enzyme responsible for converting N-acetylserotonin (NAS) in melatonin (MEL). Accordingly, we raised two hypothesis: 1) the grade of invasiveness is inversely proportional to amount of melatonin synthezised by the glioma; 2) processes that can inhibit the production of MEL by the glioma, as stimulation with pathogen-associated molecular patters (PAMPs) or pro-inflammatory cytokines, will potentiate the invasiveness of the tumor. In this project we are going to use 3 models of human glioma with different grades of aggressiveness: the more invasiveness ones (U87MG and T98G) are astrocytomas and the less invasiveness (HOG) is an oligodendroglioma. We are going to test the first hypothesis by analyzing the expression of mRNA from enzymes of MEL biosynthetic pathway (arylalkylamine N-acetyltransferases, AA-NAT; N-acetylserotonin O-methyltransferase, ASMT) and the content of MEL synthesized by cells incubated with NAS. To test the second hypothesis the same protocol is going to be used in the presence of lipopolysaccharides of Gram-negative bacteria (LPS) and tumor necrosis factor (TNF), in a way that it mimics an inflammatory response. This project is basic for understanding the role of endogenous melatonin in glioma progression, creating new perspectives for understanding the biology of tumor and for proposing therapies or using the molecule of a marker of aggressiveness.
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