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。
Effect of chemokine receptors CCR7 on disseminated behavior of human T cell lymphoma: clinical and experimental study.
机构信息
Department of Pathology, Tianjin Medical University, Tianjin, China.
出版信息
J Exp Clin Cancer Res. 2011 May 7;30(1):51. doi: 10.1186/1756-9966-30-51.
BACKGROUND
The 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.
METHODS
- 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.
RESULTS
- 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 PI(3)K, Akt and p- Akt were also observed in Hut78 than in Jurkat cell line.
CONCLUSIONS
High CCR7 expression in T-NHL cells is significantly associated with lymphatic and distant dissemination as well as with tumor cell migration and invasion in vitro. Its underlying mechanism probably involves the PI(3)K/Akt signal pathway.
背景
趋化因子受体 CCR7 的表达已在少数癌症中与肿瘤扩散和预后不良相关进行了研究。但是在非霍奇金淋巴瘤（T-NHL）中尚未进行 CCR7 表达的相关研究。本文旨在探讨 CCR7 表达与 T-NHL 进展和预后的关系。
方法
1）分析临床数据：收集 41 例 T-NHL 患者和 19 例淋巴组织增生患者的标本，并收集相应的临床病理资料。采用免疫组织化学染色法检测 CCR7、MMP-2 和 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）。用 Transwell 侵袭实验测量这两种细胞系的侵袭能力，然后研究趋化因子受体对 T-NHL 侵袭的影响及其潜在的分子机制。使用 RT-PCR 和 Western blot 评估 CCR7 的转录和表达。
结果
1）较高的 CCR7 和 MMP-9 表达比值与多发性病变和更高的 III/IV 期显著相关。此外，CCR7 和 MMP-9 表达之间存在正相关。2）在 Transwell 侵袭实验中，Hut 78 细胞系比 Jurkat 细胞系更具侵袭性。Hut78 中的 CCR7 转录和表达水平明显高于 Jurkat 细胞系。将 T-NHL 细胞系与趋化因子 CCL21 共培养，增加了 T-NHL 细胞的侵袭能力。发现 CCL21 浓度与侵袭性之间存在正相关。3）Hut78 细胞系中 PI(3)K、Akt 和 p-Akt 的转录和表达也明显高于 Jurkat 细胞系。
结论
T-NHL 细胞中 CCR7 的高表达与淋巴和远处扩散以及体外肿瘤细胞迁移和侵袭显著相关。其潜在机制可能涉及 PI(3)K/Akt 信号通路。
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