Background: The median survival time of lung cancer patients with bone metastasis is less than 6 months. Therefore, reducing the incidence of bone metastasis may provide significant clinical benefits for lung cancer patients. Whole genome expression microarray analysis indicated that the gene encoding for lumican, a protein associated with extracellular matrix interaction, was highly expressed in osteotropic lung cancer cell lines with an enhanced capacity of bone metastasis. Further experiments were conducted to reveal the role of lumican in bone metastasis of lung cancer. Methods: The expression of lumican was suppressed in the osteotropic lung cancer cells and the binding capacity to extracellular matrix components, the in vitro migration and invasion ability, and the in vivo bone metastasis capacity of these cells were examined. Exogenous lumican was provided to investigate the autocrine-regulation mechanism of lumican in the bone metastasis of lung cancer cells. Results: Transfection with lumican specific shRNA in the osteotropic lung cancer cells reduced the establishment of in vivo bone metastasis, but not lung metastasis. Reduction of lumican expression also decreased the attachment of lung osteotropic cancer cells to several extracellular matrix components and suppressed cell migration and invasion in vitro. Exogenous lumican restored these reduced capacities of lumican-knockdown cells and promoted the seeding of lung cancer cells in the bone microenvironment. Conclusion: These results suggest that lumican promotes bone metastasis of lung cancer cells through an autocrine regulatory mechanism and blocking this interaction may provide a new therapeutic approach to reduce bone metastasis in lung cancer.
