B7-H4 promotes tumor growth and metastatic progression in lung cancer by impacting cell proliferation and survival.
B7-H4 promotes tumor growth and metastatic progression in lung cancer by impacting cell proliferation and survival.
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DOI：
10.18632/oncotarget.14475
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发表时间：
2017-03-21
期刊：
影响因子：
--
通讯作者：
Huang J
中科院分区：
文献类型：
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作者：
Zhang X;Cai L;Zhang G;Shen Y;Huang J
B7-H4的异常表达发生在广泛的人类癌症中。本研究旨在探讨B7-H4在人肺癌发生转移过程中的关键作用。我们的数据显示，shrna介导的B7-H4的破坏明显抑制肿瘤细胞的增殖、侵袭和迁移，增加细胞凋亡，并在G0/G1阻滞细胞周期。这些变化伴随着Bax和caspase-3/caspase-8的显著增加，但Bcl-2、cyclinD1和AKT的激活降低。此外，我们的shrna介导的B7-H4破坏导致免疫受损小鼠肿瘤生长显著下降。重要的是，根据我们的免疫组化分析，B7-H4在我们患者队列（n = 90）中53.33%的肺癌中表达，但在任何邻近的非癌组织中均未表达。特别是B7-H4的表达似乎与淋巴结转移（P = 0.008）和TNM分期（P = 0.012）有关。综上所述，我们的研究表明B7-H4在肺肿瘤的生长、进展和转移中具有强大的促进作用，并支持其作为治疗该疾病的治疗靶点的潜力。
Aberrant expression of B7-H4 occurs across a broad spectrum of human cancers. The aim of this study was to investigate the key role of B7-H4 during tumorigenesis and metastasis of human lung cancer. Our data showed that the shRNA-mediated disruption of B7-H4 markedly inhibited tumor cell proliferation, invasion and migration, increased cell apoptosis and arrested cell cycle at G0/G1. These changes were accompanied by a marked increase in Bax and caspase-3/caspase-8, but a decrease in Bcl-2, cyclinD1 and activation of AKT. In addition, our shRNA-mediated disruption of B7-H4 led to a marked decrease in tumor growth in the immune-compromised mice. Importantly, B7-H4 was expressed in 53.33% of lung carcinomas from our patient cohort (n = 90), but not in any of adjacent non-cancerous tissues, according to our IHC analyses. In particular, B7-H4 expression appeared to be associated with lymph node metastasis (P = 0.008) and TNM stage (P = 0.012). Taken together, our study demonstrates a strong promoting role of B7-H4 in lung tumor growth, progression and metastasis, and supports its potential as a therapeutic target for the treatment of the disease.