Overexpression of matrix metalloproteinases and their inhibitors in mononuclear inflammatory cells in breast cancer correlates with metastasis-relapse.
Overexpression of matrix metalloproteinases and their inhibitors in mononuclear inflammatory cells in breast cancer correlates with metastasis-relapse.
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DOI：
10.1038/sj.bjc.6603963
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发表时间：
2007-10-08
影响因子：
8.8
通讯作者：
Vizoso, F. J.
中科院分区：
文献类型：
--
作者：
Gonzalez, L. O.;Pidal, I.;Junquera, S.;Corte, M. D.;Vazquez, J.;Rodriguez, J. C.;Lamelas, M. L.;Merino, A. M.;Garcia-Muniz, J. L.;Vizoso, F. J.
采用组织芯片和抗基质金属蛋白酶（MMP）-1、-2、-7、-9、-11、-13和-14，金属蛋白酶组织抑制剂（TIMP）-1、-2和-3的特异性抗体进行免疫组织化学研究。对131例乳腺原发性导管浸润性肿瘤患者的癌标本进行了2600多次测定。为了鉴定具有不同表达谱的特定肿瘤组，通过每种细胞类型的无监督分层聚类分析来分析数据。我们没有发现明确的肿瘤细胞或成纤维细胞的情况下集群。然而，对于单核炎症细胞，树状图显示肿瘤一级分为两种不同的MMP/TIMP分子谱，指定为第1组（n=89）和第2组（n=42）。基质金属蛋白酶-7、-9、-11、-13和-14以及TIMP-1和-2在第2组中的表达显著高于第1组。多因素分析显示，单核细胞炎性细胞聚集是与无远处复发生存率相关的最有效的独立因素（第2组：5.6（3.5-9.6），P<0.001）。我们确定了单核炎性细胞浸润肿瘤的表型，这是与远处转移的发展。因此，这一发现表明这些宿主炎性细胞可能是抑制转移的可能靶点。
An immunohistochemical study was performed using tissue microarrays and specific antibodies against matrix metalloproteinase (MMP)-1, -2, -7, -9, -11, -13 and –14, tissular inhibitors of metalloproteinase (TIMP)-1, -2 and -3. More than 2600 determinations on cancer specimens from 131 patients with primary ductal invasive tumours of the breast were performed. To identify specific groups of tumours with distinct expression profiles the data were analysed by unsupervised hierarchical cluster analysis by each cellular type. We did not find well-defined cluster of cases for tumour cells or fibroblastic cells. However, for mononuclear inflammatory cells the dendogram shows a first-order division of the tumours into two distinct MMP/TIMP molecular profiles, designated group 1 (n=89) and group 2 (n=42). Matrix metalloproteinase-7, -9, -11, -13 and -14, and TIMP-1 and -2, were identified as showing significant high expression in group 2 compared with group 1. Multivariate analysis demonstrated that clustering for mononuclear inflammatory cells was the most potent independent factor associated with distant relapse-free survival (group 2: 5.6 (3.5–9.6), P<0.001). We identify a phenotype of mononuclear inflammatory cells infiltrating tumours, which is associated with the development of distant metastasis. Therefore, this finding suggests that these host inflammatory cells could be a possible target for inhibition of metastasis.
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影响因子：
11.5
作者：
Jiang, WG;Davies, G;Mansel, RE
通讯作者：
Mansel, RE
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通讯作者：
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