Ecto-5-nucleotidase (CD73) is a potential target of hepatocellular carcinoma
Ecto-5-nucleotidase (CD73) is a potential target of hepatocellular carcinoma
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Ecto-5-核苷酸酶（CD73）是肝细胞癌的潜在靶点
DOI：
10.1002/jcp.27694
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发表时间：
2019-07-01
影响因子：
5.6
通讯作者：
Zhou, Ping
中科院分区：
文献类型：
--
作者：
Shali, Shalaimaiti;Yu, Jiangang;Zhou, Ping
据报道，在许多上皮来源的恶性肿瘤中高表达外-5-核苷酸酶（CD 73）。在这里，我们假设CD 73促进肝细胞癌（HCC）的生长和转移，这种作用是由上皮生长因子受体（EGFR）介导的。使用来自30名独立患者的具有不同恶性肿瘤的HCC细胞和肿瘤和瘤周肝组织的组织微阵列来检测CD 73和EGFR表达。采用MTT法、Ki 67检测法、细胞粘附、侵袭、迁移实验等方法检测CD 73对细胞生长和转移的影响。在抑制或过表达CD 73后，还检测了HCC细胞中EGFR的表达。最后，将皮下注射HCC细胞的裸鼠的肿瘤组织皮下移植到CD 73（-/-）和野生型（WT）C57小鼠中。CD 73在高转移肝癌细胞和癌组织中的表达高于低转移肝癌细胞和癌旁组织。在肝癌组织芯片中，CD 73和EGFR在癌组织和癌旁肝组织中共表达且呈正相关。通过质粒转染或药理学试剂上调CD 73可促进HCC细胞中EGFR的表达，而抑制CD 73可抑制这些作用。在体内实验中，移植的肿瘤组织在CD 73（-/-）小鼠中的生长明显慢于WT型小鼠。CD 73促进HCC的生长和转移，上调EGFR的表达。因此，CD 73和EGFR是治疗HCC的潜在靶点。
High expression of ecto-5-nucleotidase (CD73) has been reported in a number of epithelium origin malignancies. Here, we hypothesize that CD73 promotes hepatocellular carcinoma (HCC) growth and metastasis and that the effect is mediated by epithelial growth factor receptor (EGFR). HCC cells with different malignancies and Tissue microarrays of the tumor and peritumoral liver tissues from 30 independent patients were used to examine CD73 and EGFR expression. Then, MTT and Ki67 detection, together with cell adhesion, invasion, and migration assays were used to evaluate the effects of CD73 on cell growth and metastasis. The expression of EGFR in HCC cells was also tested after suppressing or overexpressing CD73. Lastly, tumor tissues from nude mice, which had been injected subcutaneously with HCC cells, were transplanted subcutaneously into CD73(-/-) and wild-type (WT) C57 mice. CD73 expression was higher in HCC cells with greater metastatic potentials and tumor tissues compared with low metastatic cells and peritumor tissues. CD73 and EGFR were coexpressed and positively correlated in tumor and peritumor liver tissues in HCC tissue microarrays. Up-regulationof CD73 by plasmid transfection or by pharmacological agents promoted EGFR expression in HCC cells, whereas suppression of CD73 inhibited these effects. The growth of transplanted tumor tissues was dramatically slower in CD73(-/-) mice than in WT type mice in the in vivo experiments. CD73 promotes HCC growth and metastasis and upregulated the expression of EGFR in HCC. Thus, CD73 and EGFR are potential targets in the treatment of HCC.