Apoptosis inhibition by anti-M(r) 23,000 (Thy-1) monoclonal antibodies without inducing bcl-2 expression.
Mouse malignant T-lymphoma CS-21 cells grow in vitro in the presence of CA-12 stromal cells, but they undergo apoptotic cell death with DNA fragmentation when cultured alone. Because apoptosis of CS-21 cells was not inhibited by soluble factors secreted from CA-12 stromal cells, cell-cell interactions between the two seemed to be important to inhibit apoptosis. We found that CS-21 cell adhesion was mediated by M(r) 168,000 and M(r) 23,000 proteins and that apoptosis-inhibitory signals were transmitted through these proteins. In this study, we identified the M(r) 23,000 cell adhesion molecule as a glycosylphosphatidylinositol-anchored Thy-1 (CD90) glycoprotein. Cross-linking of M(r) 23,000 protein with anti-M(r) 23,000 mAb and a second antibody transiently raised the [Ca2+]i and activated calcineurin in CS-21 cells, as has been observed in normal T lymphocytes stimulated by cross-linking anti-Thy-1 mAbs. However, differing from normal T lymphocytes, CS-21 cells could grow either by the transient increase in [Ca2+]i or by the activation of protein kinase C. Furthermore, M(r) 23,000 protein-mediated cell survival of CS-21 cells was not accompanied by expression of the apoptosis-inhibiting protein bcl-2, although protein kinase C-activated cell survival was attended by bcl-2 expression. These results indicate that the M(r) 23,000 protein (Thy-1) of CS-21 lymphoma cells functions as a cell adhesion molecule capable of transducing signals of cell survival and growth that are not followed by bcl-2 expression.
Fujita
N
N
Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.
Naito
M
M
Lee
S H
SH
Hanaoka
K
K
Tsuruo
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division; D008223:Lymphoma / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2; D017154:Stromal Cells / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2