Insights into extramedullary tumour cell growth revealed by expression profiling of human plasmacytomas and multiple myeloma
Insights into extramedullary tumour cell growth revealed by expression profiling of human plasmacytomas and multiple myeloma
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DOI：
10.1046/j.1365-2141.2003.04481.x
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发表时间：
2003-09-01
影响因子：
6.5
通讯作者：
Nimer, SD
中科院分区：
文献类型：
--
作者：
Hedvat, CV;Comenzo, RL;Nimer, SD
恶性浆细胞通常在骨髓微环境中生长；然而，它们也可以在髓外部位生长。为了确定髓外生长所需的肿瘤特异性改变，我们分析了一系列浆细胞肿瘤的表达谱，包括原发性多发性骨髓瘤（MM）、浆细胞白血病（PCL）和髓外浆细胞瘤（EPC）。层次聚类分析将 EPCs 从剩余样本中分离出来，并揭示了 EPCs 中与血管生成相关的表达模式，涉及 TIE2、NOTCH3、CD31 和内皮糖蛋白基因的较高表达。 EPC 样本与 MM 样本的直接比较发现，EPC 中有 156 个基因显着上调，85 个基因显着下调（P < 0.005，t 检验），其中包括几个涉及血管生成和粘附的基因上调（包括血管生成素 1、SPARC、Notch3 和纤连蛋白 1）。免疫组织化学染色显示 EPC 肿瘤细胞中 CD31 和内皮因子蛋白表达，它们都与血管生成相关，并且可能赋予恶性浆细胞在正常骨髓环境之外生长的能力。定义骨髓中与髓外位点如何调节恶性浆细胞生长将有助于描述肿瘤细胞生长依赖于血管生成和细胞粘附的机制。
Malignant plasma cells generally grow within the bone marrow microenvironment; however, they can also grow at extramedullary sites. To identify the tumour-specific alterations required for extramedullary growth, we analysed the expression profiles of a series of plasma cell neoplasms including primary multiple myeloma (MM), plasma cell leukaemia (PCL) and extramedullary plasmacytoma (EPC). Hierarchical clustering analysis segregated the EPCs from the remaining samples, and revealed an expression pattern associated with angiogenesis in the EPCs, involving higher expression of the genes TIE2, NOTCH3, CD31 and endoglin. Direct comparison of EPC samples with the MM samples identified 156 genes significantly upregulated and 85 genes significantly downregulated (P < 0.005, t-test) in the EPCs, including several genes involved in angiogenesis and adhesion that were upregulated (including angiopoietin 1, SPARC, Notch3 and fibronectin 1). Immunohistochemical staining demonstrated CD31 and endoglin protein expression in the EPC tumour cells, which are both angiogenesis related and could confer malignant plasma cells with the ability to grow outside the normal bone marrow environment. Defining how malignant plasma cell growth is regulated in the bone marrow versus at extramedullary sites will help to delineate the mechanisms underlying the dependence of tumour cell growth on angiogenesis and cell adhesion.