Fas/Apo-1 (CD95)-mediated apoptosis of neutrophils with Fas ligand (CD95L)-expressing tumors is crucial for induction of inflammation by neutrophilic polymorphonuclear leukocytes associated with antitumor immunity.
To address how FasL-expressing tumors induce neutrophil emigration and abrogate tumorigenicity, we investigated the behavior of FasLcDNA-transfected hepatoma MH134 (G2) cells injected into wild-type (+) mice, lpr(cg)/lpr(cg) (lpr(cg)) mice with death domain (DD)-mutated Fas, and gld/gld lpr/lpr (gld/lpr) mice with defects in FasL/Fas. G2 cells were eradicated after extensive infiltration of neutrophils around them in + mice but formed tumors without such infiltration in lpr(cg) and gld/lpr mice. Abundant cell debris suggestive of apoptosis of infiltrating neutrophils was found among G2 tumor cells in + mice but a few neutrophils infiltrating among G2 cells were intact in lpr(cg) and gld/lpr mice. Collectively, these results indicate the crucial role of Fas DD in Fas-mediated apoptosis of neutrophils and suggest that apoptosis of neutrophils with FasL-expressing tumors may trigger the extensive infiltration of neutrophils, resulting in violent inflammation and ultimately in the eradication of tumor cells.
Shimizu
M
M
Department of Molecular Oncology, Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, Honkomagome 3-18-22, Bunkyo-ku, Tokyo, 113-8613, Japan. shimizu@rinshoken.or.jp
Fontana
A
A
Takeda
Y
Y
Yoshimoto
T
T
Tsubura
A
A
Matsuzawa
A
A
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D053222:Fas Ligand Protein; D005434:Flow Cytometry / Q000379:methods; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D019463:Mice, Inbred MRL lpr; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000276:immunology*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor