Acceleration of lung metastasis by up-regulation of CD44 expression in osteosarcoma-derived cell transplanted mice

The effect of CD44-phenotypic expression on metastasis to the lung was studied using a spontaneous murine osteosarcoma-derived cell line, POS-1, stimulated with lipopolysaccharide (LPS). POS-1 cells were inoculated into the hind paws of 20 C3H/ HeJ mice and produced a visible mass in all mice in 5 weeks, and these transplanted tumors resulted in lung metastasis in all mice. The number of metastatic foci in the lungs was 12.0 +/- 2.1 (mean +/- SD) with LPS-stimulated cells, which was significantly higher than that of unstimulated cells (5.8 +/- 1.4; N = 10 for each; P < 0.05). Hyaluronate (HA), a ligand of CD44, inhibited a number of lung metastases in a dose-dependent manner (0.5% HA 3.0 +/- 1.1; 0.005% HA, 5.1 +/- 1.5; without HA, 8.6 +/- 1.7; N = 10 for each; P < 0.05, each group with HA versus the group without HA). Adhesion assay by coculturing POS-1 cells and lung microvascular endothelial cells on culture plate showed that the adhesion was significantly lower in HA treated POS-1 than those without HA (1.18 +/- 0.12 and 2.74 +/- 0.17, respectively, P < 0.05). These results suggest that lung metastasis was accelerated by up-regulation of CD44. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.