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基质金属蛋白酶 11 作为一种新型肿瘤促进因子及胰腺导管腺癌的诊断和预后生物标志物。

Matrix Metalloproteinase 11 as a Novel Tumor Promoter and Diagnostic and Prognostic Biomarker for Pancreatic Ductal Adenocarcinoma.

机构信息

From the Departments of General Surgery.

Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China.

出版信息

Pancreas. 2020 Jul;49(6):812-821. doi: 10.1097/MPA.0000000000001583.

Abstract

OBJECTIVES

Matrix metalloproteinase 11 (MMP-11) was found to be implicated in tumorigenesis in cancers. However, the significance of MMP-11 in pancreatic ductal adenocarcinoma (PDAC) is unclear.

METHODS

In the study, we detected malignant biological behaviors of pancreatic cancer after downregulation of MMP-11. Furthermore, we explored the possible mechanism, and the diagnostic value of serum MMP-11 level was analyzed in 116 patients with pathologically confirmed PDAC. In addition, we explored their prognostic value in PDAC.

RESULTS

We observed that MMP-11 could be expressed and activated in the cytoplasm of PDAC cells. Immunohistochemistry staining of PDAC tissues showed that MMP-11 was highly expressed in cancerous ductal epithelium instead of cancer stroma. We found that downregulation of MMP-11 inhibited proliferation of PDAC cell lines. The expression levels of cyclin-dependent kinase 4 and cyclin D1 were downregulated after MMP-11 knockdown. As for its clinical value, the serum level of MMP-11 was shown to be a potent promising diagnostic marker for PDAC.

CONCLUSIONS

Matrix metalloproteinase 11 may act as a tumor promoter, playing a positive role in PDAC development. Serum MMP-11 also has great potential to be a promising diagnostic marker for PDAC.

摘要

目的

基质金属蛋白酶 11(MMP-11)被发现与癌症中的肿瘤发生有关。然而,MMP-11 在胰腺导管腺癌(PDAC)中的意义尚不清楚。

方法

在这项研究中,我们检测了 MMP-11 下调后胰腺癌细胞恶性生物学行为的变化。此外,我们探讨了可能的机制,并分析了 116 例经病理证实的 PDAC 患者血清 MMP-11 水平的诊断价值。此外,我们还探讨了其在 PDAC 中的预后价值。

结果

我们观察到 MMP-11 可在 PDAC 细胞的细胞质中表达和激活。PDAC 组织的免疫组织化学染色显示,MMP-11 在癌性导管上皮中高表达,而不是在癌间质中高表达。我们发现下调 MMP-11 抑制了 PDAC 细胞系的增殖。MMP-11 敲低后,细胞周期蛋白依赖性激酶 4 和细胞周期蛋白 D1 的表达水平下调。就其临床价值而言,血清 MMP-11 水平是 PDAC 的一种潜在的有前途的诊断标志物。

结论

基质金属蛋白酶 11 可能作为肿瘤促进剂,在 PDAC 发展中发挥积极作用。血清 MMP-11 也很有潜力成为 PDAC 的一种有前途的诊断标志物。

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