Stromal cell-derived factor-1 increase αvβ3 integrin expression and invasion in human chondrosarcoma cells

✍ Scribed by Tzu-Hsiu Lai; Yi-Chin Fong; Wen-Mei Fu; Rong-Sen Yang; Chih-Hsin Tang

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 366 KB
• Volume: 218
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.21601

✦ Synopsis

Abstract

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‐1α 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‐1α also directly induced the cell surface expression of αvβ3 but not α2β1 and α5β1 integrin. Activations of ERK and NF‐κB pathways after SDF‐1 treatment was demonstrated, and SDF‐1α‐induced expression of αvβ3 integrin and invasion activity was inhibited by the specific inhibitor and mutant of ERK and NF‐κB cascades. Taken together, our results indicate that lung derived‐SDF‐1α enhances the invasiveness of chondrosarcoma cells by increasing αvβ3 integrin expression through the CXCR4/ERK/NF‐κB signal transduction pathway. J. Cell. Physiol. 218: 334–342, 2009. © 2008 Wiley‐Liss, Inc.