Cooperative regulation of non-small cell lung carcinoma angiogenic potential by macrophage migration inhibitory factor and its homolog, D-dopachrome tautomerase.
Cooperative regulation of non-small cell lung carcinoma angiogenic potential by macrophage migration inhibitory factor and its homolog, D-dopachrome tautomerase.
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DOI：
10.4049/jimmunol.181.4.2330
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发表时间：
2008-08-15
期刊：
影响因子：
--
通讯作者：
Mitchell RA
中科院分区：
文献类型：
--
作者：
Coleman AM;Rendon BE;Zhao M;Qian MW;Bucala R;Xin D;Mitchell RA
肿瘤源性生长因子和细胞因子刺激周围毛细血管的新血管生成以支持肿瘤生长。最近的研究表明，巨噬细胞移动抑制因子（MIF）的表达增加，在肺癌，特别是非小细胞肺癌（NSCLC）。由于MIF对正常和转化细胞具有重要的自分泌作用，我们研究了自分泌MIF及其唯一已知的家族成员D-多巴色素互变异构酶（D-DT）是否促进NSCLC细胞中促血管生成因子CXCL 8和VEGF的表达。我们的研究结果表明，CXCL 8和VEGF的表达强烈依赖于两个家庭成员的个人和合作活动。通过MIF和D-DT的CXCL 8转录调节似乎涉及信号传导途径，其包括c-Jun-N-末端激酶（JNK）的激活、c-Jun磷酸化和随后的AP-1转录因子活性。重要的是，与正常上清液相比，缺乏MIF和D-DT之一或两者的肺腺癌细胞的上清液诱导的人脐静脉内皮细胞（HUVEC）迁移和管形成显著减少。最后，我们证明，同源MIF受体，CD 74，是必要的MIF和D-DT诱导的JNK激活和CXCL 8的表达，这表明其潜在的参与血管生成生长因子的表达。这是首次证明D-DT的生物学作用，其与MIF的协同作用表明两个家族成员的联合治疗靶向可能会增强当前基于抗MIF的疗法。
Tumor-derived growth factors and cytokines stimulate neoangiogenesis from surrounding capillaries in order to support tumor growth. Recent studies reveal that macrophage migration inhibitory factor (MIF) expression is increased in lung cancer, particularly non-small cell lung carcinomas (NSCLC). Because MIF has important autocrine effects on normal and transformed cells, we investigated whether autocrine MIF and its only known family member, D-dopachrome tautomerase (D-DT), promote the expression of pro-angiogenic factors CXCL8 and VEGF in NSCLC cells. Our results demonstrate that the expression of CXCL8 and VEGF are strongly reliant upon both the individual and cooperative activities of the two family members. CXCL8 transcriptional regulation by MIF and D-DT appears to involve a signaling pathway that includes the activation of c-Jun-N-terminal Kinase (JNK), c-jun phosphorylation and subsequent AP-1 transcription factor activity. Importantly, human umbilical vein endothelial cell (HUVEC) migration and tube formation induced by supernatants from lung adenocarcinoma cells lacking either or both MIF and D-DT are substantially reduced when compared to normal supernatants. Finally, we demonstrate that the cognate MIF receptor, CD74, is necessary for both MIF and D-DT-induced JNK activation and CXCL8 expression, suggesting its potential involvement in angiogenic growth factor expression. This is the first demonstration of a biological role for D-DT and its synergism with MIF suggests that the combined therapeutic targeting of both family members may enhance current anti-MIF based therapies.
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影响因子：
3.7
作者：
Natarajan, R;Gupta, S;Fowler, AA
通讯作者：
Fowler, AA
DOI：
10.1073/pnas.0701553104
发表时间：
2007-08-14
影响因子：
11.1
作者：
Binsky, Inbal;Haran, Michal;Shachar, Idit
通讯作者：
Shachar, Idit
影响因子：
15.9
作者：
Arenberg, DA;Keane, MP;Strieter, RM
通讯作者：
Strieter, RM
影响因子：
82.9
作者：
Mizukami, Y;Jo, WS;Chung, DC
通讯作者：
Chung, DC
DOI：
10.1152/ajplung.00060.2002
发表时间：
2002-10-01
影响因子：
4.9
作者：
Li, J;Kartha, S;Hershenson, MB
通讯作者：
Hershenson, MB