Reciprocal interaction of cancer cells and bone marrow stroma in osteolytic bone metastasis

Tumors are complex tissues composed not only of carcinoma cells but as well of several cell types, such as fibroblasts, endothelial cells, macrophages and lymphocytes, forming the tumor-associated stroma. This microenvironment plays an important role in supporting tumor development and metastatic progression. Prostate cancer preferentially metastasizes to bone where it induces either an osteolytic (excess of bone resorption) or an osteoblastic (excess bone formation) response. Within our project we study the reactive stroma-specific expression profile of osteolytic lesions using high-throughput RNA sequencing. We take advantage of a bone metastasis model, in which human osteolytic prostate cancer cells are xenografted in the bone marrow cavity of tibiae of immunodeficient mice. RNA isolated from tumor-bearing bones consist of a mixture of mouse and human transcripts. Mouse-specific transcripts represent the stroma-specific transcriptome, whereas human-specific transcripts represent the cancer cell-specific transcriptome.