Stroeken P J, van Rijthoven E A, van der Valk M A, Roos E
Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam.
Cancer Res. 1998 Apr 1;58(7):1569-77.
Integrins have been implicated in tumor metastasis. To investigate this, we generated beta1 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 alpha4beta1 and alpha6beta1 expression, was not altered, but their metastatic capacity was greatly reduced. Tail vein injection of 10(4) 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 10(4) 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 beta1 cDNA and expressed beta1 at similar levels as ESb cells. We conclude that beta1 integrins are essential for efficient liver and spleen colonization by the ESb lymphoma.
整合素与肿瘤转移有关。为了对此进行研究，我们构建了高转移性ESb小鼠T淋巴瘤细胞系的β1整合素阴性双敲除（DKO）突变体。失去α4β1和α6β1表达的突变体在体内的生长能力未改变，但其转移能力大大降低。尾静脉注射10⁴个ESb细胞和单敲除细胞会导致所有动物在9 - 11天内死亡。相比之下，注射10⁴个DKO细胞的动物只有一半死亡，但时间要晚得多，在20 - 60天后。另一半在长达100天的时间里无病存活。ESb细胞和单敲除细胞主要转移至肝脏和脾脏，而即使经过这么长的时间，DKO细胞转移至这些器官的情况也很少见。相反，骨骼肌被广泛侵袭。一个用β1 cDNA转染并表达与ESb细胞相似水平β1的DKO克隆，其转移能力在很大程度上得以恢复。我们得出结论，β1整合素对于ESb淋巴瘤有效定植于肝脏和脾脏至关重要。
