Distal Tumors Elicit Distinctive Gene Expression Changes in Mouse Brain, Different from Those Induced by Arthritis

ABSTRACT

Tumor progression is characterized by high mutation rates, each mutation potentially generating an “alarm” signal. The brain is the main integrator of signals arising in the periphery from changes in homeostasis. We hypothesized that tumors growing at a distant site might be a stimulus strong enough to be molecularly sensed and integrated by the brain.

Transcriptome analysis of the mouse hypothalamus, midbrain, and pre-fontal cortex at different time points following administration at a distant site of mammary, lung and colon cancer cells evidenced cancer-type and brain-region specific changes in gene expression. On the contrary, no significant gene expression changes were detected in the liver. The hypothalamus was the region with the largest number of differentially expressed genes. On the array and off the array analysis of hypothalamic samples using real time PCR confirmed changes in genes associated with synaptic activity and sickness response, respectively. Gene clustering allowed the discrimination between each cancer model and between the cancer models and arthritis.

The present data provides evidence of changes in gene expression in the brain during progression of distal tumors and arthritis highlighting a potential link between distal pathological processes and the brain.