CD26 expression on T cell lines increases SDF-1-alpha-mediated invasion.
CD26 expression on T cell lines increases SDF-1-alpha-mediated invasion.
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DOI：
10.1038/sj.bjc.6605236
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发表时间：
2009-09-15
影响因子：
8.8
通讯作者：
Dang, N. H.
中科院分区：
文献类型：
--
作者：
Havre, P. A.;Abe, M.;Urasaki, Y.;Ohnuma, K.;Morimoto, C.;Dang, N. H.
CD 26是一种多功能膜结合糖蛋白，除了其其他活性外，还调节肿瘤生长。由于疾病的侵袭性与几种T细胞恶性肿瘤中的CD 26表达相关，我们决定研究表达不同水平CD 26的细胞的侵袭性。为了评估CD 26参与细胞侵袭，我们用表达不同水平CD 26的人T细胞系进行体外侵袭测定。这些包括亲本CD 26阳性T淋巴母细胞细胞系HSB-2和用表达靶向CD 26或编码错义siRNA的siRNA载体的逆转录病毒感染的克隆，以及亲本CD 26阴性T白血病细胞系Jurkat和表达CD 26的克隆。通过流式细胞术和Western免疫印迹法评价这些细胞系中的CD 26表达。CXCR 4的表达，磷酸化的信号激酶，MMP-9的分泌也进行了评估，而MMP-9的活性和激酶和CD 45抑制剂对活性的影响进行了测定条件培养基的酶谱。CD 26的存在增强了基质细胞衍生因子-1-α（SDF-1-α）介导的T细胞系的侵袭。这一过程部分受PI-3 K和MEK 1通路调节，如在SDF-1-α存在下p44/42 MAP激酶和Akt的磷酸化增加以及它们各自的抑制剂对MMP-9分泌和体外侵袭的影响所示。此外，当CD 45被抑制时，CD 26相关的SDF-1-α诱导的侵袭增强作用降低。我们的研究结果表明，在体外系统中，T细胞系中CD 26的表达导致SDF-1-α介导的侵袭增加，并且这部分受PI-3 K和MEK 1途径控制。这些数据还表明，CD 26增强侵袭可能是由CD 45介导的，然而，需要更多的研究来证实这种参与。
CD26 is a multifunctional membrane-bound glycoprotein that regulates tumour growth in addition to its other activities. Because disease aggressiveness is correlated with CD26 expression in several T-cell malignancies, we decided to investigate the invasiveness of cells expressing different levels of CD26. To assess CD26 involvement in cell invasion, we performed in vitro invasion assays with human T cell lines expressing different levels of CD26. These included the parental CD26-positive T-lymphoblast cell line HSB-2 and clones infected with a retrovirus expressing siRNA vectors that either targeted CD26 or encoded a missense siRNA, and the parental CD26-negative T-leukaemia cell line Jurkat and clones expressing CD26. CD26 expression in these cell lines was evaluated by flow cytometry and western immunoblotting. CXCR4 expression, phosphorylation of signalling kinases, and MMP-9 secretion were also evaluated by western immunoblotting, whereas MMP-9 activity and the effect of kinase and CD45 inhibitors on activity were measured by zymography of conditioned media. The presence of CD26 enhanced stromal-cell-derived factor-1-α (SDF-1-α)-mediated invasion of T cell lines. This process was regulated in part by the PI-3K and MEK1 pathways, as indicated by increased phosphorylation of p44/42 MAP kinase and Akt in the presence of SDF-1-α and the effect of their respective inhibitors on MMP-9 secretion and in vitro invasion. In addition, CD26-associated enhancement of SDF-1-α-induced invasion was decreased when CD45 was inhibited. Our results indicate that the expression of CD26 in T cell lines leads to increased SDF-1-α-mediated invasion in an in vitro system and that this is controlled in part by the PI-3K and MEK1 pathways. The data also suggest that CD26 enhancement of invasion may be mediated by CD45, however, more studies are required to confirm this involvement.
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影响因子：
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作者：
CARBONE, A;GLOGHINI, A;PINTO, A
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