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Association of CXCR1 and 2 expressions with gastric cancer metastasis in ex vivo and tumor cell invasion in vitro

机译：CXCR1和2表达与胃癌体外转移及体外肿瘤细胞侵袭的关系

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Background: CXCR1 and CXCR2, cell surface receptors of interleukin-8, regulate cell migration and alteration of their expression has been associated with poor prognosis of various cancers. The aim of this study was to detect their expression in gastric cancer to identify associations with another cell adhesion molecule, matrix metalloproteinase-9 (MMP9), and with clinicopathological data ex vivo, and then explore their potential role in gastric cancer cells in vitro. Materials and methods: A total of 172 cases of gastric cancer tissue specimens were collected for immunohistochemical analysis of CXCR1, CXCR2, and MMP9 expression. Expression of CXCR1 and CXCR2 proteins was knocked in or down using their cDNA and shRNA, respectively, in gastric cancer cell lines to assess the changed cell phenotypes and gene expression. Results: CXCR1, CXCR2, and MMP9 were expressed in 61.0%, 77.9%, and 75.6% of gastric cancer tissues, respectively. Moreover, CXCR1 and CXCR2 expression was associated with tumor differentiations, advanced clinical stages, lymph node, and distant metastasis of gastric cancer. Similarly, MMP9 expression was associated with CXCR1 and CXCR2. Expression of these three proteins was interrelated. In vitro study showed that levels of CXCR1 and CXCR2 proteins were associated with the capacity of gastric cancer cell migration, while knockdown of their expression inhibited gastric cancer cell migration and invasion abilities in vitro. In contrast, overexpression of CXCR1 and CXCR2 proteins promoted tumor cell migration and invasion. At the gene levels, knockdown of CXCR1 or CXCR2 expression suppressed expression of Ets-1, SRC-1, and JNK proteins and phosphorylated c-Jun and Erk1/2. Conversely, upregulation of CXCR1 or CXCR2 promoted expression of Ets-1, SRC-1, JNK, and c-Jun proteins and phosphorylated JNK, c-Jun and Erk1/2. Conclusions: These findings suggest that CXCR1 and CXCR2 play an important role in gastric cancer progression. Further study will be performed to investigate whether target of their expression can be used as a novel strategy in clinical control of gastric cancer metastasis.
机译：背景：白细胞介素8的细胞表面受体CXCR1和CXCR2调节细胞迁移及其表达的改变与各种癌症的不良预后有关。这项研究的目的是检测它们在胃癌中的表达，以鉴定与另一种细胞粘附分子基质金属蛋白酶9（MMP9）的关系，以及与离体临床病理数据的联系，然后探讨其在体外胃癌细胞中的潜在作用。材料与方法：收集172例胃癌组织标本，进行CXCR1，CXCR2和MMP9表达的免疫组化分析。使用CXCR1和CXCR2蛋白的cDNA和shRNA分别敲除或敲除胃癌细胞系中的表达，以评估改变的细胞表型和基因表达。结果：CXCR1，CXCR2和MMP9分别在胃癌组织中的表达率为61.0％，77.9％和75.6％。此外，CXCR1和CXCR2的表达与胃癌的肿瘤分化，临床分期，淋巴结转移和远处转移有关。同样，MMP9表达与CXCR1和CXCR2相关。这三种蛋白质的表达是相互关联的。体外研究表明，CXCR1和CXCR2蛋白的水平与胃癌细胞迁移的能力有关，而敲低它们的表达则抑制了胃癌细胞的迁移和侵袭能力。相反，CXCR1和CXCR2蛋白的过表达促进肿瘤细胞的迁移和侵袭。在基因水平上，敲低CXCR1或CXCR2的表达抑制Ets-1，SRC-1和JNK蛋白的表达以及磷酸化的c-Jun和Erk1 / 2。相反，CXCR1或CXCR2的上调促进Ets-1，SRC-1，JNK和c-Jun蛋白的表达以及磷酸化的JNK，c-Jun和Erk1 / 2的表达。结论：这些发现表明CXCR1和CXCR2在胃癌的进展中起重要作用。将进行进一步的研究，以研究其表达的靶点是否可以用作临床控制胃癌转移的新策略。

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