Chemokine receptor CXCR4-β1 integrin axis mediates tumorigenesis of osteosarcoma HOS cells

Abstract

It is known that β1 integrins mediate the migratory response of cells to chemokine stimulation. Also, both β1 integrins and chemokines have roles in tumor development. In the present study, the β1 integrin-chemokine axis is assessed using human osteosarcoma (HOS) transfectant cells expressing the CXCR4 receptor for chemokine SDF-1 (CXCL12). We first identified in vitro the specific β1 integrins that mediated the migratory response to SDF-1 stimulation. Results showed that on collagen type I and laminin, the chemotactic response to SDF-1 was predominantly mediated by α2β1 integrin. On fibronectin, SDF-1-stimulated chemotaxis involved both α4β1 and α5β1 integrins. A comparison of the transfectant clones expressing CXCR4 at low, intermediate, and high levels and the control transfectant revealed that the transfectant clones migratory response in vitro and their ability to form tumors in vivo was related to their levels of CXCR4 expression. In addition, treatment by injection with mAbs to CXCR4, integrin α2β1, or integrin α5β1 effectively inhibited the growth of HOS-CXCR4 transfectant cells in vivo. Therefore, our results show that the β1 integrins that mediated the migratory response were also functionally linked to the enhanced tumor growth of CXCR4-expressing HOS transfectant cells.Key words: integrins, chemokines, chemotaxis, osteosarcoma, tumorigenesis.