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Suppression of T-Lymphoma Cell Apoptosis by Monoclonal Antibodies Raised against Cell Surface Adhesion Molecules¹

Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113 [N. F., S. K., M. N., N. B., M. N., T. T.], and Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 1-37-1, Kami-Ikebukuro, Toshimaku, Tokyo 170 [Y. H., T. T.], Japan

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.

¹ This study was supported in part by grants from the Ministry of Education, Science and Culture, Japan, and the Special Coordination Fund of the Science and Technology Agency, Japan.

² To whom requests for reprints should be addressed, at Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113, Japan.

Received 4/20/93. Accepted 8/ 6/93.

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