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尿激酶型纤溶酶原激活物和细胞外基质蛋白的表达增强与多发性骨髓瘤的进展有关。

Augmented expression of urokinase plasminogen activator and extracellular matrix proteins associates with multiple myeloma progression.

机构信息

Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India.

出版信息

Clin Exp Metastasis. 2014 Jun;31(5):585-93. doi: 10.1007/s10585-014-9652-7. Epub 2014 May 8.

Abstract

Multiple myeloma (MM) represents a B cell malignancy, characterized by a monoclonal proliferation of malignant plasma cells. Interactions between tumor cells and extracellular matrix (ECM) are of importance for tumor invasion and metastasis. Protein levels of urokinase plasminogen activator (uPA) and fibulin 1, nidogen and laminin in plasma and serum respectively and mRNA levels of these molecules in peripheral blood mononuclear cells were determined in 80 subjects by using ELISA and quantitative PCR and data was analyzed with severity of disease. Pearson correlation was determined to observe interrelationship between different molecules. A statistical significant increase for ECM proteins (laminin, nidogen and fibulin 1) and uPA at circulatory level as well as at mRNA level was observed compared to healthy controls. The levels of these molecules in serum might be utilized as a marker of active disease. Significant positive correlation of all ECM proteins with uPA was found and data also correlates with severity of disease. Strong association found between ECM proteins and uPA in this study supports that there might be interplay between these molecules which can be targeted. This study on these molecules may help to gain insight into processes of growth, spread, and clinical behavior of MM.

摘要

多发性骨髓瘤(MM)是一种 B 细胞恶性肿瘤,其特征是恶性浆细胞的单克隆增殖。肿瘤细胞与细胞外基质(ECM)之间的相互作用对于肿瘤的侵袭和转移很重要。通过 ELISA 和定量 PCR 分别在 80 名受试者的血浆和血清中测定了尿激酶纤溶酶原激活物(uPA)和纤连蛋白 1、巢蛋白和层粘连蛋白的蛋白水平,以及外周血单个核细胞中这些分子的 mRNA 水平,并根据疾病严重程度进行了数据分析。通过 Pearson 相关性分析观察不同分子之间的相互关系。与健康对照组相比,在循环水平和 mRNA 水平上均观察到 ECM 蛋白(层粘连蛋白、巢蛋白和纤连蛋白 1)和 uPA 的水平显著升高。这些分子在血清中的水平可作为疾病活动的标志物。所有 ECM 蛋白与 uPA 之间均存在显著正相关,且数据与疾病严重程度相关。本研究中 ECM 蛋白与 uPA 之间存在强烈关联,表明这些分子之间可能存在相互作用,可以作为治疗靶点。对这些分子的研究可能有助于深入了解 MM 的生长、扩散和临床行为过程。

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