Fas expression inversely correlates with metastatic potential in osteosarcoma cells.
A complex series of steps must take place to allow for a single cell to metastasize. Identifying factors responsible for these steps is essential in developing targeted therapy. We developed series of osteosarcoma cell lines with differing metastatic potentials. We used them to investigate mechanisms of metastasis and possible therapeutic targets for osteosarcoma metastasis to the lung in a nude mouse model. No correlation was found between epidermal growth factor receptor (EGFR), insulin-like growth factor receptor inhibitor (IGF-I-R), gelatinase, p53, metalloproteinase 9 (MMP 9), platelet derived growth factor receptor (PDGF-R), vascular endothelial growth factor (VEGF) and c-met expression and metastatic potential as measured by Northern analysis. By contrast, Fas expression inversely correlated with metastatic potential, and manipulation of Fas expression altered the metastatic phenotype of the cell. Our data indicate that fas gene expression may offer a new therapeutic target for the treatment of metastatic osteosarcoma in the lung.
Worth
Laura L
LL
Department of Pediatrics, M.D. Anderson Cancer Center, Houston, TX 77030, USA. lworth@mdanderson.org
Lafleur
Elizabeth A
EA
Jia
Shu-Fang
SF
Kleinerman
Eugenie S
ES
D000818:Animals; D017209:Apoptosis; D015152:Blotting, Northern; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D016228:Endothelial Growth Factors / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D018093:Gelatinases / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary*; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D012516:Osteosarcoma / Q000378:metabolism / Q000556:secondary*; D010957:Plasmids; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019014:fas Receptor / Q000378:metabolism*
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019014:fas Receptor; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met; D017526:Receptor, IGF Type 1; D017479:Receptors, Platelet-Derived Growth Factor; D018093:Gelatinases; D020780:Matrix Metalloproteinase 9