Suppression of T-lymphoma cell apoptosis by monoclonal antibodies raised against cell surface adhesion molecules.
We have previously established a mouse malignant T-lymphoma CS-21 cell line that preferentially metastasizes to lymph nodes after s.c. inoculation into BALB/c mice. The CS-21 lymphoma cells were grown in vitro in the presence of CA-12 stromal cells isolated from lymph nodes. When CS-21 cells were cultured alone, they underwent apoptotic cell death with DNA fragmentation. In contrast, the culture of CS-21 cells attached to a monolayer of CA-12 stromal cells prevented CS-21 cell apoptosis and enhanced cell proliferation. To identify the cell adhesion molecules, we developed monoclonal antibodies (mAbs) directed against CS-21 cell surface proteins. Fourteen mAbs partially inhibited the binding of CS-21 cells to a CA-12 stromal cell monolayer. MCS-5 (mAb against CS-21 No. 5) directed against a M(r) 168,000 cell membrane protein and MCS-19 against a M(r) 23,000 protein were found to suppress apoptosis and to stimulate CS-21 cell growth. Soluble factors secreted from CA-12 stromal cells enhanced CS-21 cell growth but were not sufficient to prevent apoptosis. In the presence of both stromal cell-secreted factors and mAbs MCS-5 or MCS-19, CS-21 lymphoma cells evaded apoptosis and grew as fast as in the coculture with CA-12 stromal cells. Because of these results, we conclude that CA-12 lymph node stromal cells support CS-21 lymphoma cell growth by secreting paracrine growth factors and by presenting receptors for the M(r) 168,000 and M(r) 23,000 cell surface adhesion molecules of CS-21 cells that transmit signals to prevent CS-21 cell apoptosis.
Fujita
N
N
Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.
Kataoka
S
S
Naito
M
M
Heike
Y
Y
Boku
N
N
Nakajima
M
M
Tsuruo
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D007700:Kinetics; D016399:Lymphoma, T-Cell / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules