The expression of CXCR4, CXCL12 and CXCR7 in malignant pleural mesothelioma.
The expression of CXCR4, CXCL12 and CXCR7 in malignant pleural mesothelioma.
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DOI：
10.1002/path.2829
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发表时间：
2011-03
影响因子：
7.3
通讯作者：
You, Liang
中科院分区：
文献类型：
--
作者：
Li, Tong;Li, Hui;Wang, Yucheng;Harvard, Chansonette;Tan, Jia-Li;Au, Alfred;Xu, Zhidong;Jablons, David M.;You, Liang
趋化因子CXCL 12及其受体CXCR 4和CXCR 7参与肿瘤进展、转移和存活。我们研究了CXCR 4、CXCL 12和CXCR 7在恶性胸膜间皮瘤中的表达，以确定它们是否是可能的生物标志物和潜在的治疗靶点。41例间皮瘤肿瘤组织、10例正常人胸膜组织和2例间皮瘤细胞系用抗CXCR 4、抗CXCL 12、抗CXCR 7和抗β-Akt抗体染色。采用RT-PCR方法检测CXCR 4、CXCL 12和CXCR 7在6种人间皮瘤细胞系（H28、211 H、H2052、ms-1、H290和H513）和1种人正常间皮瘤细胞系LP 9中的表达。这七种细胞系也用抗CXCR 7染色。我们发现CXCR 4和CXCL 12在97.6%和78.0%的间皮瘤组织样品中表达，同时p-Akt强表达（R2分别为0.739和0.620）。此外，间皮瘤组织中CXCR 7的表达弱于CXCR 4的表达。此外，RT-PCR显示CXCR 4和CXCL 12在5/6个间皮瘤细胞系（211 H、H2052、ms-1、H290和H513）中过表达，而CXCR 7仅在2/6个间皮瘤细胞系（H513和H2052）中过表达。此外，我们发现CXCR 4拮抗剂AMD 3100抑制所有5种过表达CXCR 4和CXCL 12的间皮瘤细胞系的生长。我们的研究结果表明，Akt-mTOR通路参与了这五个间皮瘤细胞系中CXCL 12/CXCR 4轴的中断。总之，CXCR 4和CXCL 12在大多数间皮瘤细胞系和肿瘤组织中高度表达，表明CXCR 4和CXCL 12可用作间皮瘤患者的生物标志物。CXCL 12-CXCR 4相互作用可能是间皮瘤的潜在治疗靶点。
The chemokine CXCL12 and its receptors, CXCR4 and CXCR7, are involved in tumor progression, metastasis, and survival. We investigated the expression of CXCR4, CXCL12 and CXCR7 in malignant pleural mesothelioma to determine if they are possible biomarkers and potential therapeutic targets. Forty-one mesothelioma tumor tissues, 10 normal human pleural tissues and 2 mesothelioma cell lines were stained with anti-CXCR4, anti-CXCL12, anti-CXCR7 and anti-p-Akt antibodies. RT-PCR was performed to determine the expression of CXCR4, CXCL12 and CXCR7 in 6 human mesothelioma cell lines (H28, 211H, H2052, ms-1, H290, and H513) and 1 human normal mesothelial cell line LP9. These seven cell lines were also stained with anti-CXCR7. We found that CXCR4 and CXCL12 were expressed in 97.6% and 78.0% mesothelioma tissue samples, concurrent with strong expression of p-Akt (R2 = 0.739 and 0.620 respectively). In addition, CXCR7 expression was weaker than CXCR4 expression in mesothelioma tissues. Furthermore, RT-PCR showed that CXCR4 and CXCL12 were over-expressed in 5/6 mesothelioma cell lines (211H, H2052, ms-1, H290, and H513), whereas CXCR7 was over-expressed in only 2/6 (H513 and H2052). Moreover, we found that the CXCR4 antagonist AMD3100 inhibited the growth of all 5 mesothelioma cell lines that over-express CXCR4 and CXCL12. Our results suggest that the Akt-mTOR pathway is involved during the interruption of the CXCL12/CXCR4 axis in these five mesothelioma cell lines. In conclusion, CXCR4 and CXCL12 are highly expressed in most mesothelioma cell lines and tumor tissues, suggesting that CXCR4 and CXCL12 may be used as biomarkers for patients with mesothelioma. The CXCL12-CXCR4 interaction may be a potential therapeutic target for mesothelioma.
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