Predominant role of alpha 4-integrins for distinct steps of lymphoma metastasis.
To analyze the role of alpha4-integrins in lymphoma metastasis, sublines of the T-cell lymphoma LB were generated by retrovirus-mediated gene transfer that differ exclusively in the expression of alpha4-integrins. Using LB-alpha4 and control LB-NTK cells, we demonstrate that expression of alpha4-integrins strongly suppresses metastasis formation of LB lymphoma cells in secondary lymphoid organs such as spleen, mesenteric and peripheral lymph nodes, or Peyer's patches after i.v. injection into syngeneic BALB/c mice. Moreover, alpha4-integrin expression inhibited development of metastatic tumors in liver, lung, and kidney. Expansion of LB lymphoma cells in bone marrow was not affected by alpha4-integrin expression. In vivo migration assays using 51Cr-labeled lymphoma cells demonstrated that low-metastatic LB-alpha4 cells accumulated with the same efficiency as high-metastatic LB-NTK cells in all target organs examined and were even enriched in mucosal lymphoid organs. Collectively, these results indicate that alpha4-integrins inhibit metastasis formation of lymphoma cells at a stage subsequent to the invasion of target organs.
Gosslar
U
U
Institute for Medical Microbiology and Hygiene, Technical University, Munich, Germany.
Jonas
P
P
Luz
A
A
Lifka
A
A
Naor
D
D
Hamann
A
A
Holzmann
B
B
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D039441:Integrin alpha4; D016023:Integrins / Q000502:physiology*; D016399:Lymphoma, T-Cell / Q000209:etiology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D016023:Integrins; D039441:Integrin alpha4