LACK OF TUMORIGENICITY OF INTERLEUKIN-4 AUTOCRINE GROWING CELLS SEEMS RELATED TO THE ANTITUMOR FUNCTION OF INTERLEUKIN-4
LACK OF TUMORIGENICITY OF INTERLEUKIN-4 AUTOCRINE GROWING CELLS SEEMS RELATED TO THE ANTITUMOR FUNCTION OF INTERLEUKIN-4
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DOI：
10.1016/0161-5890(90)90039-3
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发表时间：
1990-12-01
影响因子：
3.6
通讯作者：
BLANKENSTEIN, T
中科院分区：
文献类型：
--
作者：
LI, WQ;DIAMANTSTEIN, T;BLANKENSTEIN, T
最近，白细胞介素4 （IL4）自分泌生长的CT4S细胞在体内生长失败已被证实。由于不能排除细胞产生的IL4不足以支持其在体内的生长，因此建立了对外源IL4无反应的亚克隆，因此获得了完全的生长自主性。从亚克隆注射到裸鼠体内同样没有产生肿瘤的事实来看，我们可以得出结论，自分泌生长的CT4S产生的IL4阻止了它们在体内的生长。为了验证这一假设，我们构建了一种在免疫球蛋白重链（Igh）增强子/启动子控制下含有il - 4基因的逆转录病毒载体，并将其用于感染骨髓瘤细胞系J558L。建立了IL4产生克隆（J558L- xepil4），并在裸鼠中监测肿瘤与亲本克隆J558L的进展情况。IL4的产生显著延缓了J558L-XEPIL4在体内的生长。将J558L-XEPIL4细胞注射到同基因BALB/c小鼠体内，肿瘤抑制作用更为明显。这些结果可以解释为什么自分泌生长的CT4S不能在体内生长，并提示功能性T淋巴细胞参与宿主依赖的il - 4抗肿瘤作用的有效性。
Recently, the failure of interleukin 4 (IL4) autocrine growing CT4S cells to grow in vivo has been demonstrated. Because it could not be excluded that the cells produce insufficient amounts of IL4 to support their growth in vivo, subclones were established which are unresponsive to exogenous IL4 and therefore have acquired full growth autonomy. From the fact that the subclones likewise did not give rise to tumors when injected into nude mice, one may conclude that the IL4 production of autocrine growing CT4S prevents their growth in vivo. To test this hypothesis, a retroviral vector containing the IL4 gene under the control of the immunoglobulin heavy chain (Igh) enhancer/promoter was constructed and used to infect the myeloma cell line J558L. An IL4 producing clone was established (J558L-XEPIL4) and the tumor progression in comparison to the parental clone J558L was monitored in nude mice. The IL4 production significantly delayed the growth of J558L-XEPIL4 in vivo. Tumor suppression was much more evident when J558L-XEPIL4 cells were injected into syngeneic BALB/c mice. These results may explain why autocrine growing CT4S do not grow in vivo and suggest the involvement of functional T lymphocytes in the effectiveness of the host dependent anti-tumor action of IL4.