Adaptation of breast cancer cells to brain, bone marrow, and lung tissue

The Her-2/Neu-positive mouse breast cancer cell line was serially co-cultured with minced brain, bone marrow, and lung tissue in an intravital microscopy chamber mounted on the dorsal skinfold of nude mice, alternating with growth in vitro. Gene expression analysis was performed on the cells grown in culture after sorting and further growth in vitro. Gene expression under these growth conditions differed in time and according to the co-cultivated organ tissue. This study reveals genes that are expressed by cells as they adapt differentially to various foreign tissue microenvironments, and may represent a paradigm to discover gene expression changes that occur immediately upon extravasation when cancer metastasizes. Gene expression analysis was performed for four time points and three tissues, brain, bone marrow, and lung, using Affymetrix microarrays. Technical replicates of the array analysis were performed for the brain samples. Biological replicates were performed for the first two brain time points, and one passage of N202 cells on breast tissue was analyzed.