Molecular profiling of functional interactions between pre-osteoblastic and breast carcinoma cells

The relationships between cancer cells and the microenvironment play a critical role in cancer growth and development. The bone stroma consists of mesenchymal stem cells (MSCs) and mature osteoblasts that promote cancer growth. Yet it is not completely understood what are the molecular processes guiding cancer cells progression to the bone. In this study, a co-culture assay and subsequent gene profiling arrays were used to compare the gene expression profile of a pre-osteoblastic cell line (MBA-15) with that of a mammary adenocarcinoma (DA3) cells. Following co-culture, cells were separated by magnetic beads based on the expression of CD326 antigen. RNA was purified and hybridized on gene expression array. The gene expression pattern changes were followed by qRT-PCR. We demonstrate that co-cultured DA3 cells express elevated levels of genes that regulate growth and responses to both hormonal stimulus and wounding, as well as reduced expression of genes related to lipid metabolism. Also, co-cultured pre-osteoblastic cells showed reduced expression of cell-junction genes. The study presents a simplified model system, composed of pre-osteoblastic and mammary cancer cells, that potentially mimics the molecular interactions in the tumor microenvironment which contribute to tumor-progression.

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Glait-Santar C, Pasmanik-Chor M, Oron-Karni V, Benayahu D