TWEAK mediates anti-tumor effect of tumor-infiltrating macrophage
TWEAK mediates anti-tumor effect of tumor-infiltrating macrophage
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DOI：
10.1016/j.bbrc.2005.03.176
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发表时间：
2005-06-03
影响因子：
3.1
通讯作者：
Okumura, K
中科院分区：
文献类型：
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作者：
Kaduka, Y;Takeda, K;Okumura, K
TWEAK诱导多种细胞反应。包括促炎趋化因子的产生、迁移、增殖和通过TWEAK受体Fn14的细胞死亡。在本研究中，我们检测了肿瘤细胞中TWEAK或fn14表达对肿瘤生长的影响。中和anti-TWEAK mAb可显著降低肿瘤排斥反应的频率，缩短小鼠腹腔接种表达tweak敏感Fn 14的肿瘤细胞的存活时间。此外，抗tweak单抗处理促进了表达tweak敏感Fn 14的肿瘤细胞的皮下生长，这种促进作用通过抑制巨噬细胞浸润而非NK细胞消耗而被消除。相反，抗tweak单抗处理对表达Fn 14的tweak耐药肿瘤细胞的生长没有明显影响，即使肿瘤细胞表达Fn 14。另一方面，在肿瘤细胞中表达TWEAK对皮下肿瘤生长无显著影响，这些结果表明TWEAK在体内介导了巨噬细胞的抗肿瘤作用。(c) 2005爱思唯尔公司版权所有。
TWEAK induces diverse cellular responses. including pro-inflammatory chemokine productions migration, proliferation, and cell death through the TWEAK receptor, Fn14. In the present Study we examined the effect of TWEAK or Fn 14 expression in tumor cells on tumor outgrowth in vivo. Administration of neutralizing anti-TWEAK mAb significantly reduced the frequency of tumor rejection and shortened the survival of mice intraperitoneally inoculated with TWEAK-sensitive Fn 14-expressing tumor cells. Moreover, anti-TWEAK mAb treatment promoted the subcutaneous growth of TWEAK-sensitive Fn 14-expressing tumor cells, and this promotion was abolished by the inhibition of macrophage infiltration but not NK cell depletion, In contrast, administration of anti-TWEAK mAb had no apparent effect on the growth of TWEAK-resistant tumor cells, even if tumor cells expressed Fn 14. On the other hand, TWEAK expression in tumor cells had no significant effect on subcutaneous tumor growth, These result, indicate that TWEAK mediates anti-tumor effect of macrophages in vivo. (c) 2005 Elsevier Inc. All rights reserved.