Predominant role of alpha 4-integrins for distinct steps of lymphoma metastasis.

Abstract

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.

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@article{Gosslar1996PredominantRO, title={Predominant role of alpha 4-integrins for distinct steps of lymphoma metastasis.}, author={U. Gosslar and P. Jonas and Arne Luz and A Lifka and David Naor and Alf Hamann and Bernhard Holzmann}, journal={Proceedings of the National Academy of Sciences of the United States of America}, year={1996}, volume={93 10}, pages={4821-6} }