Functional pathways shared by liver and lung metastases: a mitochondrial chaperone machine is up-regulated in...

Genes that mediate breast cancer metastasis to lung are different from those which mediate bone metastasis. However, which markers accounts for the diversity of breast cancer metastasis remains unknown. The aim of this study was identify proteins associated with the soft-tissue metastatic ability of breast cancer tumors in metastases, coupling microarray data from clinical metastases and immunohistochemistry, for further screening for early detection at the first diagnosis in patients. We use a bioinformatic program to create and analyze protein interaction networks from protein experimental data, and to translate RNA expression analysis of breast cancer human metastases to protein, in a search for the phenotype associated with soft-tissue metastases. The pre-validated proteins constituted the protein signature for each metastasis: 37 (8.9%) from liver, 92 (8.5%) from lung and 167 (13%) from bone. Pleiotrophin, BAG 2, HSP 60 and vinculin were pre-validated in liver and lung metastases performing the soft-tissue phenotype. After IHC validation, we conclude that HSP 60, one of the best-known mitochondrial chaperone machines, is a key protein in soft-tissue metastases phenotype interacting with BAG 2, which competes for binding to GRP 75, the other mitochondrial chaperone. The relationship between HSP 60/GRP 75 and BAG 2 might result in the activation of several transcription pathways, different in liver from in lung metastases, as a nodal point coupling positive and negative actuators in the multiple survival-signal pathways and so achieving metastatic growth.