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首页> 外文期刊>Developmental immunology >Proteolytic activity of human lymphoid tumor cells. Correlation with tumor progression.
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Proteolytic activity of human lymphoid tumor cells. Correlation with tumor progression.

机译:人淋巴瘤细胞的蛋白水解活性。与肿瘤进展相关。

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Matrix metalloproteinase (MMP) expression and production are associated with advanced-stage tumor and contribute to tumor progression, invasion and metastases. The current study was designed to determine the expression and production of MMP-2 (gelatinase A) and MMP-9 (gelatinase B) by human lymphoid tumor cells. Changes in expression and production were also investigated during tumor progression of multiple myeloma and mycosis fungoides. In situ hybridization analysis revealed that lymphoblastic leukemia B cells (SB cell line), multiple myeloma (MM) cells (U266 cell line) and lymphoblastic leukemia T cells (CEM and Jurkat cell lines) express constitutively the mRNA for MMP-2 and/or MMP-9. We demonstrated by gelatin-zymography of cell culture medium that both enzymes were secreted in their cleaved (activated) form. In situ hybridization of bone marrow plasma cells and gelatin-zymography of the medium showed that patients with active MM (diagnosis, relapse, leukemic progression) express higher levels of MMP-2 mRNA and protein than patients with non-active MM (complete/objective response, plateau) and with monoclonal gammopathies of undetermined significance (MGUS). MMP-9 expression and secretion was similar in all patient groups. In patients with mycosis fungoides (MF), the expression of MMP-2 and MMP-9 mRNAs was significantly upregulated with advancing stage, in terms of lesions both positive for one of two mRNAs and with the greatest intensity of expression. Besides MF cells, the MMP-2 and/or MMP-9 mRNAs were expressed by some stromal cell populations (microvascular endothelial cells, fibroblasts, macrophages), suggesting that these cells cooperate in the process of tumor invasion. Our studies identify MMPs as an important class of proteinases involved in the extracellular matrix (ECM) degradation by human lymphoid tumors, and suggest that MMPs inhibitors may lead to important new treatment for their control.
机译:基质金属蛋白酶(MMP)的表达和产生与晚期肿瘤有关,并有助于肿瘤的进展,侵袭和转移。本研究旨在确定人淋巴瘤细胞对MMP-2(明胶酶A)和MMP-9(明胶酶B)的表达和产生。在多发性骨髓瘤和真菌病真菌的肿瘤进展过程中还研究了表达和产生的变化。原位杂交分析显示淋巴母细胞白血病B细胞(SB细胞系),多发性骨髓瘤(MM)细胞(U266细胞系)和淋巴母细胞白血病T细胞(CEM和Jurkat细胞系)组成性表达MMP-2和/或MMP-9。我们通过细胞培养基的明胶酶法证实,两种酶均以其裂解(激活)的形式分泌。骨髓浆细胞的原位杂交和培养基的明胶酶谱分析表明,活动性MM(诊断,复发,白血​​病进展)的患者表达的MMP-2 mRNA和蛋白水平高于非活动性MM(完全/客观) (高原反应)和具有不确定性的单基因游戏(MGUS)。在所有患者组中,MMP-9的表达和分泌均相似。在蕈样真菌病(MF)患者中,就两个mRNA之一均为阳性且表达强度最大的病变而言,MMP-2和MMP-9 mRNA的表达随发展阶段显着上调。除了MF细胞外,一些基质细胞群(微血管内皮细胞,成纤维细胞,巨噬细胞)还表达了MMP-2和/或MMP-9 mRNA,这表明这些细胞在肿瘤侵袭过程中起着协同作用。我们的研究确定MMPs是人类淋巴瘤参与细胞外基质(ECM)降解的重要一类蛋白酶,并且表明MMPs抑制剂可能导致对其控制的重要新治疗方法。

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