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结直肠癌中的Syndecan-1、上皮-间质转化标志物(E-钙黏蛋白/β-连环蛋白)和新生血管生成相关蛋白(PCAM-1和内皮糖蛋白)

Syndecan-1, Epithelial-Mesenchymal Transition Markers (E-cadherin/β-catenin) and Neoangiogenesis-related Proteins (PCAM-1 and Endoglin) in Colorectal Cancer.

作者信息

Mitselou Antigony, Galani Vassiliki, Skoufi Urania, Arvanitis Dimitris L, Lampri Evangeli, Ioachim Elli

机构信息

Department of Forensic Pathology, Medical School, University of Ioannina, Ioannina, Greece

Department of Anatomy-Histology- Embryology, Medical School, University of Ioannina, Ioannina, Greece.

出版信息

Anticancer Res. 2016 May;36(5):2271-80.

Abstract

The Syndecan-1 protein plays a crucial role in cell proliferation, cell adhesion, cell migration and angiogenesis and, at the same time, its co-expression with E-cadherin is regulated during epithelial-mesenchymal transition (EMT). In colorectal cancer (CRC), the expression of syndecan-1, E-cadherin/β-catenin complex is frequently disturbed. Angiogenesis is critical for the growth and metastatic spread of tumors. In the present study, we focused on the expression of these biological molecules and their prognostic significance in human CRC. Formalin-fixed paraffin-embedded surgical specimens from 69 patients with CRC were immunostained for syndecan-1, E-cadherin, β-catenin, endoglin (CD105) and CD31 (platelet cell adhesion molecule (PCAM-1)). A significant association was found between syndecan-1 with E-cadherin (p<0.0001), as well with β-catenin (p<0.0001). High β-catenin expression appeared to reduce the risk of poor outcome. Endoglin microvascular density (MVD) count was correlated significantly with Dukes' stage (p<0.0001), vessel invasion (p<0.0001), lymph node metastasis (p=0.039), liver metastasis (p<0.0001), recurrence of disease (p=0.010) and poor survival rate (p<0.0001). Endoglin tumor epithelial cell expression was associated with E-cadherin, β-catenin and syndecan-1 (p=0.001, p=0.068 and p=0.005, respectively). In conclusion, changes in the pattern of expression of syndecan-1, EMT markers, E-cadherin/β-catenin, in association with endoglin (CD105), may be involved in tumor progression and prognosis of CRC patients. Further studies are needed to clarify the interaction between these proteins and tumor initiation and progression.

摘要

Syndecan-1蛋白在细胞增殖、细胞黏附、细胞迁移和血管生成中发挥着关键作用,同时,在上皮-间质转化(EMT)过程中,其与E-钙黏蛋白的共表达受到调控。在结直肠癌(CRC)中,Syndecan-1、E-钙黏蛋白/β-连环蛋白复合物的表达经常受到干扰。血管生成对于肿瘤的生长和转移扩散至关重要。在本研究中,我们关注这些生物分子在人类CRC中的表达及其预后意义。对69例CRC患者的福尔马林固定石蜡包埋手术标本进行免疫染色,检测Syndecan-1、E-钙黏蛋白、β-连环蛋白、内皮糖蛋白(CD105)和CD31(血小板细胞黏附分子(PCAM-1))。发现Syndecan-1与E-钙黏蛋白之间存在显著关联(p<0.0001),与β-连环蛋白之间也存在显著关联(p<0.0001)。高β-连环蛋白表达似乎降低了不良预后的风险。内皮糖蛋白微血管密度(MVD)计数与Dukes分期(p<0.0001)、血管侵犯(p<0.0001)、淋巴结转移(p=0.039)、肝转移(p<0.0001)、疾病复发(p=0.010)和低生存率(p<0.0001)显著相关。内皮糖蛋白在肿瘤上皮细胞中的表达与E-钙黏蛋白、β-连环蛋白和Syndecan-1相关(分别为p=0.001、p=0.068和p=0.005)。总之,Syndecan-1、EMT标志物、E-钙黏蛋白/β-连环蛋白的表达模式变化,与内皮糖蛋白(CD105)相关,可能参与CRC患者的肿瘤进展和预后。需要进一步研究来阐明这些蛋白质与肿瘤发生和进展之间的相互作用。

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