Analise de possiveis mecanismos e consequencias funcionais da expressão de galectina-3 em celulas de glioma expostas a condições hipoxicas / Analysis of possible mechanisms and functional consequences of galectin-3 expression in glioma cells exposed to hypoxia

AUTOR(ES)
DATA DE PUBLICAÇÃO

2009

RESUMO

Gliomas are primary Central Nervous System tumors. Among them, glioblastomas are the most common clinical forms and have the worst prognosis. In an attempt to understand glioma biology, the NG97 cell line was established. This cell line presents glioblastoma s characteristics, showing nuclear atipia and high growth rate. Recently, it was discovered that this is a human-murine hybrid cell line derived from the fusion between human astrocytoma and murine stroma cells that likely occurred in the process of cell line establishment. The cell line was therefore renamed NG97ht. This cell line grows as tumors in immunodeficient mice displaying histopathological characteristics of pseudopalisades commonly seen in glioblastomas. These areas are comprised by hypercellular regions in the edge of necrotic environments and are possibly constituted by actively migrating cells out of necrotic/hypoxic environments. Besides, these pseudopalisades show the expression of molecules related to adaptation to oxygen deprivation, like Hypoxia Inducible Factor (HIF), which is involved in cell survival through the induction of many genes. Also, it has been shown that under hypoxia, galectin-3 production is stimulated, a protein involved in diverse cellular processes and that is only present in these pseudopalisades in glioblastomas, not being detected in its adjacent areas. Galectin-3 is a lectin that binds to beta-galactosides and is related to increased motility, adhesion, tumor growth and progression. Also, studies describe that galectin-3 expression is related to its promoter methylation degree in some tumor types. Our results presented here demonstrated that assays performed in hypoxic chamber and in a chemical condition mimicking hypoxia (incubation with cobaltous chloride) showed galectin-3 induction in either complete medium or deprived of fetal bovine serum, mimicking tumor s necrotic areas deprived of oxygen and nutrients. Besides, it was demonstrated that galectin-3 modulation in vitro and in vivo is not due to promoter methylation. Tests related to galectin-3 knockdown in oxygen and nutrient deprivation demonstrated that this protein has a key role in protection against cell death. It is possible that these results may indicate that galectin-3 can also protect tumor cells inside glioblastoma s necrotic areas, acting as a survival factor in disadvantageous environments with low concentrations of oxygen and nutrients. In conclusion, these experiments demonstrate galectin-3 properties related to protection against cell death in environments deprived of oxygen and nutrients, commonly found inside tumors, highlighting its importance as a target to antineoplastic agents.

ASSUNTO(S)

galectin 3 cellular hypoxia pseudopaliçada ng97ht pseudopalisading galectina gliomas ng97ht glioma

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