Galectin-3 (gal-3) is a β-galactoside binding protein related to many tumoral aspects, e.g. angiogenesis, cell growth and motility and resistance to cell death. Evidence has shown its upregulation upon hypoxia, a common feature in solid tumors such as glioblastoma multiformes (GBM). This tumor presents a unique feature described as pseudopalisading cells, which accumulate large amounts of gal-3. Tumor cells far from hypoxic/nutrient deprived areas express little, if any gal-3. Here, we have shown that the hybrid glioma cell line, NG97ht, recapitulates GBM growth forming gal-3 positive pseudopalisades even when cells are grafted subcutaneously in nude mice. In vitro experiments were performed exposing these cells to conditions mimicking tumor areas that display oxygen and nutrient deprivation. Results indicated that gal-3 transcription under hypoxic conditions requires previous protein synthesis and is triggered in a HIF-1α and NF-κB dependent manner. In addition, a significant proportion of cells die only when exposed simultaneously to hypoxia and nutrient deprivation and demonstrate ROS induction. Inhibition of gal-3 expression using siRNA led to protein knockdown followed by a 1.7–2.2 fold increase in cell death. Similar results were also found in a human GBM cell line, T98G. In vivo, U87MG gal-3 knockdown cells inoculated subcutaneously in nude mice demonstrated decreased tumor growth and increased time for tumor engraftment. These results indicate that gal-3 protected cells from cell death under hypoxia and nutrient deprivation in vitro and that gal-3 is a key factor in tumor growth and engraftment in hypoxic and nutrient-deprived microenvironments. Overexpression of gal-3, thus, is part of an adaptive program leading to tumor cell survival under these stressing conditions.

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Ao meu orientador, Prof. Dr. Roger Chammas, por todos os inestimáveis ensinamentos, pelo exemplo de profissional e ser humano e por sempre acreditar em mim, desde o primeiro instante. À Dra. Camila Machado, por compartilhar tantos conhecimentos comigo durante todos os anos do mestrado e doutorado, por sua amizade especial, por sempre me apoiar e incentivar nos momentos mais difíceis. Por sempre estar presente, mesmo fisicamente distante. Ao Dr. Fu-Tong Liu por ter me recebido de maneira tão acolhedora em seu laboratório e pela experiência inigualável que tive em Taipei. Ao Dr. Huan-Yuan Chen por todo o auxílio e cuidado. À Annie, pela preciosa ajuda na rotina do laboratório. Ao saudoso Prof. Dr. Francesco Langone, pelo exemplo de vida e por ter me guiado para este caminho. Aos queridos amigos de laboratório Adalberto, Alexandre, Ana Carol, Andréia,

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