Een niet-metabolische rol van aspartaat in de vorming van longmetastasen

Metabolic priming of the pre-metastatic niche supports lung metastasis formation 2.1 million cases of breast cancer are diagnosed every year, making it the most frequent cancer among women. Once breast cancers have metastasized they almost certainly result in patient mortality. On top of that, it is unknown how to inhibit metastatic growth or breast cancers. Thus, we have no effective treatment for ~25% of the patients. This is a direct consequence of our limited knowledge of the molecular events that confer metastatic ability to breast cancer cells. Emerging evidence shows that the secondary organ microenvironment is shaped by the primary tumor through the release of factors already before the metastatic onset, favouring the formation of a "pre-metastatic niche". This permissive environment is mainly characterized by extracellular matrix (ECM) remodeling and recruitment of pro-tumor immune cells. However, little is known about the nutrient composition of the pre-metastatic organ and whether this affects metastasis formation. Therefore, I will investigate the role of nutrients in priming the pre-metastatic site and I will evaluate whether the accumulation of specific metabolites favour metastatic seeding and growth. The information I will obtain will contribute to fill the gap in our understanding of how the microenvironment changes before metastasis formation, with the aim to favour the establishment of metastasis. On the long term perspective, this will contribute to understand the potential of therapeutic strategies that target the nutrient microenvironment before metastasis formation, leading to novel effective options for the treatment of metastasizing TNBC, which is -up to date- incurable.