Fas and Fas ligand interactions suppress melanoma lung metastasis.
Apoptosis induced by Fas (CD95) ligation is frequently lost during tumor progression; however, there is no direct evidence to support an association of Fas loss-of-function with metastatic tumor behavior. To determine whether Fas loss-of-function is critical for acquisition of the metastatic phenotype, we have compared the ability of Fas-sensitive K1735 murine melanomas to form spontaneous lung metastases in wild-type and Fas ligand-deficient mice. Fas-sensitive melanoma clones are highly tumorigenic but rarely metastatic in wild-type syngeneic mice. However, in Fas ligand-deficient mice, both the incidence and number of metastases are increased. These findings provide the first evidence that Fas-Fas ligand interactions can suppress metastasis and that tumor Fas loss-of-function may be causally linked to metastatic progression.
Owen-Schaub
L B
LB
Department of Immunology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. lowensch@mdanderson.org
van Golen
K L
KL
Hill
L L
LL
Price
J E
JE
D000818:Animals; D017209:Apoptosis; D053222:Fas Ligand Protein; D008024:Ligands; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology / Q000556:secondary*; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000556:secondary*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor