Effect of chemokine receptors CCR7 on disseminated behavior of human T cell lymphoma: clinical and experimental study.

Effect of chemokine receptors CCR7 on disseminated behavior of human T cell lymphoma: clinical and experimental study.
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趋化因子受体CCR7对人T细胞淋巴瘤播散行为的影响:临床和实验研究

DOI:
10.1186/1756-9966-30-51
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发表时间:
2011-05-07
期刊:
Journal of experimental & clinical cancer research : CR
影响因子:
--
通讯作者:
Sun B
Sun B
中科院分区:
其他
文献类型:
--
作者:
Yang J;Wang S;Zhao G;Sun B

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研究背景趋化因子受体CCR 7的表达与肿瘤扩散和少数肿瘤预后不良有关。尚未对非霍奇金淋巴瘤(T-NHL)中CCR 7的表达进行此类研究。本研究旨在探讨CCR 7表达与T-NHL进展及预后的关系。方法1)临床资料分析:收集T-NHL患者41例,淋巴样增生患者19例。同时收集相应的临床病理资料。免疫组化法检测CCR 7、MMP-2、MMP-9的表达水平。2)培养人T-NHL细胞系Hut 78(皮肤T细胞淋巴瘤)和Jurkat(成人T细胞白血病/淋巴瘤)。采用Transwell侵袭实验检测两种细胞系的侵袭能力,研究趋化因子受体对T-NHL侵袭能力的影响及其分子机制。结果(1)多发性乳腺癌患者中CCR 7和MMP-9的表达率明显高于非多发性乳腺癌患者(P < 0. 05)。CCR 7与MMP-9的表达呈正相关。2)在Transwell侵袭测定中,Hut 78细胞系比Jurkat细胞更具侵袭性。CCR 7在Hut 78细胞中的转录和表达水平均显著高于Jurkat细胞。将T-NHL细胞系与趋化因子CCL 21共培养,增加T-NHL细胞的侵袭力。结论T-NHL细胞中CCL 21的高表达与淋巴结转移、远处转移以及肿瘤细胞的迁移和侵袭密切相关。其机制可能与PI 3 K/Akt信号通路有关。
BackgroundThe expression of chemokine receptors CCR7 has been studied in relation to tumor dissemination and poor prognosis in a limited number of cancers. No such studies have been done on CCR7 expression in non-Hodgkin's lymphoma (T-NHL). Our aim in this paper is to investigate the association between CCR7 expression and progression and prognosis of T-NHL.Methods1) Analysis of clinical data: The specimens were obtained from 41 patients with T-NHL and 19 patients with lymphoid hyperplasia. Their corresponding clinicopathologic data were also collected. The expression levels of CCR7, MMP-2, and MMP-9 were examined by immunohistochemical staining. 2) Human T-NHL cell lines Hut 78 (cutaneous T-cell lymphoma) and Jurkat (adult T-cell leukemia/lymphoma) were cultured. The invasiveness of the two cell lines were measured with a Transwell invasion assay, and then used to study the effects of chemokine receptors on T-NHL invasion and the underlying molecular mechanism. The transcript and expression of CCR7 were evaluated using RT-PCR and western blotting.Results1) The higher CCR7 and MMP-9 expression ratios were significantly associated with multiple lesions and higher stage III/IV. Moreover, a positive correlation was observed between CCR7 and MMP-9 expression. 2) The Hut 78 cell line was more invasive than the Jurkat cells in the Transwell invasion assay. The transcript and expression levels of CCR7 were significantly higher in Hut78 than that of Jurkat cell line. The T-NHL cell lines were co-cultured with chemokine CCL21 which increased the invasiveness of T-NHL cell. The positive association between CCL21 concentration and invasiveness was found. 3) The stronger transcript and expression of PI3K, Akt and p- Akt were also observed in Hut78 than in Jurkat cell line.ConclusionsHigh CCR7 expression in T-NHL cells is significantly associated with lymphatic and distant dissemination as well as with tumor cell migration and invasionin vitro. Its underlying mechanism probably involves the PI3K/Akt signal pathway.
DOI: 10.1084/jem.188.2.373
发表时间: 1998-07-20
影响因子: 15.3
作者:
Dieu, M C;Vanbervliet, B;Vicari, A;Bridon, J M;Oldham, E;Ait-Yahia, S;Briere, F;Zlotnik, A;Lebecque, S;Caux, C
通讯作者: Caux, C
DOI: 10.1074/jbc.273.12.7118
发表时间: 1998-03-20
影响因子: 4.8
作者:
Yoshida, R;Nagira, M;Yoshie, O
通讯作者: Yoshie, O
DOI: 10.1084/jem.194.12.1875
发表时间: 2001-12-17
期刊: The Journal of experimental medicine
影响因子: --
作者:
Henning G;Ohl L;Junt T;Reiterer P;Brinkmann V;Nakano H;Hohenberger W;Lipp M;Förster R
通讯作者: Förster R
DOI: 10.1038/35065016
发表时间: 2001-03-01
期刊: NATURE
影响因子: 64.8
作者:
Müller, A;Homey, B;Zlotnik, A
通讯作者: Zlotnik, A
DOI: 10.1093/jnci/93.21.1638
发表时间: 2001-11-07
期刊: JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子: --
作者:
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通讯作者: Hwang, ST