[Lymphatic metastasis and cell adhesion, growth and growth inhibition].
Malignant tumor cells often metastasize to regional and distant lymph nodes. The mechanisms of lymphatic metastasis, however, have not been well understood. To investigate these mechanisms, we used mouse CS-21 malignant T lymphoma cells which form tumors at subcutaneous sites and metastasize to lymph nodes with a high incidence. In contrast, CS-21 cells do not metastasize to other organs following intravenous injection. CS-21 lymphoma cells continuously grew in vitro when the cells were cocultured with CA-12 stromal cells isolated from lymph nodes. However, when CS-21 cells were separated from the stromal cells, they underwent apoptosis which was characterized by nucleus condensation and DNA fragmentation. We have developed monoclonal antibodies against CS-21 cell surface molecules by intrasplenic injection of the cell membranes. Several clones of monoclonal antibodies were able to partially inhibit adhesion of CS-21 cells to a monolayer of CA-12 stromal cells. Treatment of CS-21 cells with the monoclonal antibodies which specifically bind to the cell surface components of M(r) -168K and -23K prevented the apoptosis of CS-21 cells after separation from the stromal cells. In the experiments using Transwell chambers we found that the growth of CS-21 cells was also supported by soluble factors secreted from CA-12 stromal cells. The secreted factors were, however, not sufficient to prevent CS-21 cell apoptosis. The result suggested that the stromal cells of lymph nodes play an important role in lymphatic metastasis of CS-21 lymphoma cells by cell-cell adhesion and secretion of soluble factors that prevent apoptosis of lymphoma cells and enhance their growth in concert.
Fujita
N
N
Institute of Applied Microbiology, University of Tokyo.
Kataoka
S
S
Tsuruo
T
T
D000818:Animals; D000911:Antibodies, Monoclonal; D017209:Apoptosis; D002448:Cell Adhesion; D016923:Cell Death; D002455:Cell Division; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000473:pathology*; D016399:Lymphoma, T-Cell / Q000473:pathology*; D051379:Mice; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal