Elevated expression of phosphatidylserine in the outer membrane leaflet of human tumor cells and recognition by activated human blood monocytes.
We determined whether the presence of phosphatidylserine (PS) in the outer membrane leaflet of human tumor cells correlated with their recognition by activated human monocytes. Three tumorigenic cell lines, A375 melanoma and A431 and Colo-16 carcinomas, and a normal human epidermal keratinocyte line (NHEK) were incubated with monocytes activated to the tumoricidal state by gamma-interferon and lipopolysaccharide. Activated human monocytes bound to and lysed all tumorigenic targets, while the nontumorigenic NHEK were neither bound nor killed. Semiquantitative analysis of PS in the outer leaflet of the cells revealed that the tumorigenic cells expressed 3-7-fold more PS than did the nontumorigenic NHEK. To determine whether enhanced PS expression on the tumor cells was responsible for their recognition by activated monocytes, NHEK were supplemented with exogenously supplied analogues of PS and phosphatidylcholine. PS-labeled NHEK but not phosphatidylcholine-labeled nor control NHEK bound to activated human monocytes. These results suggest a role for PS in monocyte recognition of tumor cells.
Utsugi
T
T
Department of Cell Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Schroit
A J
AJ
Connor
J
J
Bucana
C D
CD
Fidler
I J
IJ
D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002448:Cell Adhesion; D003110:Colonic Neoplasms / Q000378:metabolism*; D006801:Humans; D008545:Melanoma / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D009000:Monocytes / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D010587:Phagocytosis; D010718:Phosphatidylserines / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D008565:Membrane Proteins; D009363:Neoplasm Proteins; D010718:Phosphatidylserines