profiling of liver from mice s.c. injected with LL/2(LLC1) lung carcinoma cells vs. PBS

The main function of the nervous system is to maintain homeostasis by sensing and reacting to signals that reach a certain threshold. For example, the brain can sense immune peripheral events through soluble compounds or the vagus nerve and can react through activation of the hypothalamus-pituitary-adrenal axis, resulting in the modulation of an ongoing immune response. Cancer progression is characterized by high mutation rates, with each mutation potentially promoting alarm signals during the 10 to 15 years of cancer development before clinical detection. It is not known, however, whether the brain can recognize the presence of a peripheral tumour, and if this recognition can be molecularly assessed. Using genome-wide expression analysis in three mouse tumour models, we show that a tumor growing at the periphery can indeed promote changes in the expression levels of defined sets of genes in the brain, but not in the liver. These changes are cancer type - and brain region-specific, occur as early as 18 h after tumour cell injection, involve specific signalling pathways and differ from changes in gene expression induced during arthritis. The brain and specially the hypothalamus can discriminate among different cancer types and between cancer and arthritis by expressing specific sets of genes, highlighting the role of specific brain regions as early sensors of signals emanating from chronic peripheral diseases. These findings prove that cancer-derived signals are effective in eliciting specific changes in gene expression in discrete brain regions and open a question regarding the potential role of brain genes in cancer outcomes Keywords: gene expression profile of the liver in response to peripheral tumor cells We used two-color oligonucleotides in-house printed microarrays in a case-control direct design with two technical replicates in a dye swap design. We analyzed 3 different time points: 18, 72 and 192 h after tumor cells or PBS injection. We performed 4 samples (biological replicates) for the three time points.