Emmprin, a cell surface inducer of matrix metalloproteinases (MMPs), is expressed in T-cell lymphomas
Emmprin, a cell surface inducer of matrix metalloproteinases (MMPs), is expressed in T-cell lymphomas
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DOI：
10.1002/path.1518
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发表时间：
2004-03-01
影响因子：
7.3
通讯作者：
Kikuchi, M
中科院分区：
文献类型：
--
作者：
Nabeshima, K;Suzumiya, J;Kikuchi, M
基质金属蛋白酶（MMPs）降解细胞外基质是肿瘤侵袭和转移的关键步骤。在人类癌症中，已经证明肿瘤细胞-成纤维细胞相互作用（TFI）在肿瘤中MMP水平的上调中起作用，并且细胞外基质金属蛋白酶诱导因子是肿瘤细胞上的表面分子，其刺激附近的成纤维细胞产生MMP-1、2和3。T细胞淋巴瘤经常表现出淋巴结器官受累和皮肤侵袭，但TFI在其侵袭中的作用尚未详细研究。本研究调查了TFIs在T细胞淋巴瘤与emmprin表达和MMP生产特别参考。免疫组化结果显示，非肿瘤性淋巴结（10例）中仅有生发中心细胞和部分组织细胞表达emmprin，而所有T细胞淋巴瘤（14例成人T细胞白血病淋巴瘤（ATLL），6例淋巴母细胞性淋巴瘤，7例间变性大细胞淋巴瘤，9例血管免疫母细胞性T细胞淋巴瘤）均呈强阳性和弥漫性表达。正常人外周血的流式细胞仪分析显示，小部分的B细胞，T细胞和单核细胞表达emmprin，而emmprin表达T细胞的数量大大增加，并表达这种蛋白质到一个更高的水平，在ATLL患者。在体外共培养的emmprin阳性HTLV-1转化的淋巴细胞（MT-2）和emmprin阴性的人成纤维细胞增强生产的pro-MMP-2（明胶酶A）和活性MMP-2，与单独的细胞类型的文化。这种刺激被抑制的活性阻断肽对emmprin。此外，在ATL皮肤受累患者的组织病理学切片中，在浸润ATL细胞周围的成纤维细胞中发现了MMP-2，但在非病变区域的成纤维细胞中未发现。总之，emmprin是过表达的T淋巴瘤细胞，与正常的同行相比，并促进MMP-2的生产通过与成纤维细胞，这可能发挥了作用，淋巴瘤细胞的间质入侵的相互作用。版权所有（C）2004大不列颠和爱尔兰病理学会。出版社：John Wiley Sons，Ltd
Degradation of the extracellular matrix by matrix metalloproteinases (MMPs) is a crucial step in tumour invasion and metastasis. In human carcinomas, tumour cell-fibroblast interactions (TFIs) have been demonstrated to play a role in the up-regulation of MMP levels in tumours, and emmprin is a surface molecule on tumour cells that stimulates nearby fibroblasts to produce MMP-1, 2, and 3. T-cell lymphomas frequently show extranodal organ involvement and skin invasion, but a role for TFIs in their invasion has not been examined in detail. This study investigated TFIs in T-cell lymphomas with special reference to emmprin expression and MMP production. Immunohistochemically, only germinal centre cells and some histiocytes expressed emmprin in non-neoplastic lymph nodes (ten cases), while all T-cell lymphomas [14 cases of adult T-cell leukaemia-lymphoma (ATLL), six cases of lymphoblastic lymphoma, seven cases of anaplastic large cell lymphoma, and nine cases of angio-immunoblastic T-cell lymphoma] expressed emmprin strongly and diffusely. FACS analysis of peripheral blood from normal individuals revealed that small fractions of B-cells, T-cells, and monocytes expressed emmprin, whereas emmprin-expressing T-cells were much increased in number, and expressed this protein to a higher level, in ATLL patients. In vitro co-cultures of emmprin-positive HTLV-1-transformed lymphocytes (MT-2) and emmprin-negative human fibroblasts enhanced the production of pro-MMP-2 (gelatinase A) and active MMP-2, compared with cultures of either cell type alone. This stimulation was inhibited by an activity-blocking peptide against emmprin. Moreover, in histopathological sections from patients with ATL skin involvement, MMP-2 was demonstrated in fibroblasts around infiltrating ATL cells, but not in fibroblasts in non-diseased areas. In conclusion, emmprin is overexpressed by T-lymphoma cells, when compared with normal counterparts, and facilitates MMP-2 production via interactions with fibroblasts, which could play a role in stromal invasion by lymphoma cells. Copyright (C) 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley Sons, Ltd.