Characterizing the Tumor Suppressor Role of CEACAM1 in Multiple Myeloma
Characterizing the Tumor Suppressor Role of CEACAM1 in Multiple Myeloma
复制标题
表征 CEACAM1 在多发性骨髓瘤中的肿瘤抑制作用
DOI：
10.1159/000487730
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Wu, Depei
中科院分区：
文献类型：
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作者：
Xu, Jinge;Liu, Bin;Wu, Depei
背景/目的：癌胚抗原相关细胞黏附分子1(CEACAM1)，又称CD66a，是免疫球蛋白(Ig)超家族的一员，属于癌胚抗原(CEA)家族，在癌症中具有双重作用。以往研究表明CEACAM1在多发性骨髓瘤(MM)中高表达。本研究旨在探讨CEACAM1在骨肉瘤细胞中过表达的生物学效应。方法：将pEGFP-N1-CEACAM1和pcDNA3.1-CEACAM1表达载体分别导入U-266和RPMI8266细胞。CCK8比色法检测CEACAM1过表达对两株细胞增殖的影响。用AnnexinV-FITC/PI流式细胞仪检测CEACAM1转染后细胞周期和细胞凋亡的变化。Hoest染色证实细胞凋亡的变化。Western blotting检测caspase-3活性。细胞侵袭和迁移活性的变化分别通过Well小室实验和伤口愈合实验进行。Western blotting检测基质金属蛋白酶2、9蛋白的表达。用流式细胞仪对50例新诊断的症状性多发性骨髓瘤(MM)患者骨髓中的骨髓瘤细胞进行免疫表型分析。研究各组间CEACAM1表达水平与临床特征的相关性。结果：CEACAM1过表达可显著抑制MM细胞增殖，诱导细胞凋亡，抑制细胞侵袭和迁移，其机制可能是通过激活caspase-3和下调MMP2和MMP9来实现的。DS分期I期患者CEACAM1表达频率(61.5%)高于DS II期患者(21.1%)和DS III期患者(22.2%)。此外，β2-微球蛋白水平等于或小于3.5 mg/L的MM患者的β表达高于CEACAM1水平>3.5 mg/L的患者。结论：CEACAM1可能是MM中的一种肿瘤抑制因子。
Background/Aims: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), also known as CD66a, is a member of the immunoglobulin (Ig) superfamily that belongs to the carcinoembryonic antigen (CEA) family which plays a dual role in cancer. Previous studies showed high expression of CEACAM1 in multiple myeloma (MM). The aim of this study was to investigate the biological consequences of CEACAM1 overexpression in MM. Methods: pEGFP-N1-CEACAM1 and pcDNA3.1-CEACAM1 expression plasmids were transfected into U-266 and RPMI8266 cell lines . Effect of CEACAM1 overexpression on the proliferation of two cell lines were tested by the CCK8 assay. Cell cycle and Apoptotic changes after CEACAM1 transfection were examined with AnnexinV–FITC/PI by flow cytometry. Hochest staining assay was used to confirm the apoptotic changes. Caspase-3 activity was examined by Western blotting. The cell invasion and migration activity change after CEACAM1 transfection were performed by well chamber assays and a wound healing, respectively. MMP-2 and MMP-9 proteins expression were detected by Western blotting. Flow cytometry immunophenotyping was be evaluated on myeloma cells from bone marrow taken from 50 patients with symptomatic MM newly diagnosed. The correlations between CEACAM1 expression levels and the clinical features across all groups were investigated. Results: CEACAM1 overexpression significantly suppressed MM cell proliferation, induced cell apoptosis, and inhibited cell invasion and migration possibly through activation of caspase-3 and downregulation of MMP-2 and MMP-9. CEACAM1 expression in patients with DS stage I was more frequent (61.5%) than those with DS stage II (21.1%) or III (22.2%). Furthermore, patients with β2-microglobulin levels equal to or less than 3.5 mg/L had higher CEACAM1 expression than those with β2-microglobulin levels greater than 3.5 mg/L. Conclusion: Our findings suggest that CEACAM1 may act as a tumor suppressor in MM.