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.
Shiratori
H
H
Department of Orthopaedic Surgery, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. hiro-s@qc4.so-net.ne.jp
Koshino
T
T
Uesugi
M
M
Nitto
H
H
Saito
T
T
D000818:Animals; D002448:Cell Adhesion; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000502:physiology; D018960:Hyaluronan Receptors / Q000378:metabolism*; D008070:Lipopolysaccharides; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary*; D051379:Mice; D008809:Mice, Inbred C3H; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
D018960:Hyaluronan Receptors; D008070:Lipopolysaccharides