Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. The stromal cell-derived factor 1 (SDF-1), constitutively secreted by human lung epithelium cells, has been shown to function in a key role for recruitment of neutrophils. Here, we found that human chondrosarcoma tissues and chondrosarcoma cell lines had significant expression of CXCR4 (SDF-1 receptor), which was higher than normal cartilage and human chondrocyte. SDF-1alpha and lung epithelium cells conditioned medium (LECM) induced the invasiveness of chondrosarcoma cells. SDF-1 siRNA inhibited LECM-induced invasion of chondrosarcoma cells and SDF-1alpha also directly induced the cell surface expression of alphavbeta3 but not alpha2beta1 and alpha5beta1 integrin. Activations of ERK and NF-kappaB pathways after SDF-1 treatment was demonstrated, and SDF-1alpha-induced expression of alphavbeta3 integrin and invasion activity was inhibited by the specific inhibitor and mutant of ERK and NF-kappaB cascades. Taken together, our results indicate that lung derived-SDF-1alpha enhances the invasiveness of chondrosarcoma cells by increasing alphavbeta3 integrin expression through the CXCR4/ERK/NF-kappaB signal transduction pathway.
(c) 2008 Wiley-Liss, Inc.