Abstract
Integrins have been implicated in tumor metastasis. To investigate this, we generated β1 integrin-negative double knockout (DKO) mutants of the highly metastatic ESb murine T-lymphoma cell line. The in vivo growth capacity of the mutants, which had lost α4β1 and α6β1 expression, was not altered, but their metastatic capacity was greatly reduced. Tail vein injection of 104 ESb and single-knockout cells led to death of all animals within 9–11 days. In contrast, only one-half of the animals injected with 104 DKO cells died, but much later, after 20–60 days. The other one-half remained disease-free for up to 100 days. Whereas ESb and single-knockout cells disseminated predominantly to liver and spleen, metastasis of DKO cells to these organs was rare, even after this prolonged period. Instead, skeletal muscles were invaded extensively. Metastatic capacity was largely restored in a DKO clone, which had been transfected with β1 cDNA and expressed β1 at similar levels as ESb cells. We conclude that β1 integrins are essential for efficient liver and spleen colonization by the ESb lymphoma.
Footnotes
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↵1 To whom requests for reprints should be addressed, at Division of Cell Biology, The Netherlands Cancer Institute, 121 Plesmanlaan, 1066 CX Amsterdam, the Netherlands. Phone: 31-20-5121931; Fax: 31-20-5121944; E-mail: eroos@nki.nl.
- Received October 3, 1997.
- Accepted February 2, 1998.
- ©1998 American Association for Cancer Research.
Volume 58, Issue 7
