Gene expression in cancer cells is influenced by contact with bone cells in a novel coculture system that models bone metastasis.

Abstract

Contact between bone cells and cancer cells (heterotypic cell contact) is thought to play a central role in the initial growth and progression of metastatic cells. Attempts at studying heterotypic contact in vitro and in vivo have been confounded by difficulty in controlling how and when heterotypic contact occurs between unlike cells. A novel model, the micropatterned coculture system, is described that quantifies and controls heterotypic contact between cancer cells and bone cells in vitro. The micropatterned coculture system is biocompatible, and is modified easily to accommodate two or more different populations of cells. Immunofluorescence of cocultures of prostate cancer-3 cells and osteoblasts show the precise control of cell interactions. Ribonucleic acid of sufficient quantity and quality is isolated readily from cells cocultured on the micropatterned coculture system. The expression of the metastasis associated genes urokinase plasminogen activator, insulinlike growth factor binding protein-1 and insulinlike growth factor binding protein-3 are regulated in response to heterotypic contact and soluble factors respectively. A model of bone metastasis based on the micropatterned coculture system technology will streamline the process for testing therapeutic agents, so that more molecules can be identified for animal and clinical testing at less cost and in less time than using conventional methods.