趋化因子受体CCR7在T细胞淋巴瘤播散中的作用

The Role of Chemokine Receptor CCR7 in Dissemination of T Cell Lymphoma

目的:探讨趋化因子受体CCR7在T细胞淋巴瘤播散中的作用;旨在为T细胞淋巴瘤靶点治疗的新方向提供一定的实验基础及理论依据。方法:皮肤T细胞淋巴瘤Hut78和成人T淋巴细胞白血病/淋巴瘤Jurkat细胞株培养,通过Transwell小室检测了细胞体外侵袭能力并进行比较;通过RT-PCR和Western-blot技术对两种细胞株的CCR7和PI_3K/A kt信号转导通路的表达进行了检测。结果:1)Hut78细胞体外侵袭能力较强;两种T细胞淋巴瘤细胞经过CCL21共培养后,侵袭能力均有所增强,且均呈现与CCL21浓度的正相关趋势;2)Hut78细胞中CCR7mRNA,PI_3KmRNA、AktmRNA均高于Jurkat细胞,差异均有显著性(P<0.001);CCR7、pAkt蛋白在Hut78细胞中的表达也明显高于Jurkat细胞(P<0.05)。结论:T细胞淋巴瘤中高表达的CCR7与肿瘤的侵袭性有关,可能通过PI_3K/Akt信号通路促进肿瘤的侵袭和播散。

Objective： To explore the role and mechanisms of chemokine receptors in the T-cell lymphoma invasion process in order to provide experimental and theoretical basis for target therapy of T-cell lymphoma. Methods： The cutaneous T-cell lymphoma Hut78 and adult T-cell leukemia/lymphoma Jurkat cell lines were co-cultured. The in vitro invasive ability of the two cell lines was measured by Transwell invasion assay. The transcription and expression of CCR7 and key enzymes in PI3K/Akt pathway were evaluated using RT-PCR and Western blot. Results： Hut78 cell lines showed a stronger invasive ability in the Transwell assay. After the two cell lines were co-cultured with chemokine CCL21, their invasive ability was increased. The invasive ability displayed a positive correlation with the CCL21 concentration. The CCR7 mRNA, PI3K mRNA and Akt mRNA expression was all higher in Hut78 cell line than in Jurkat cell line, with significant differences （ P 〈 0.001 ）. The expression of CCR7 and pAkt protein was significantly higher in Hut78 cell line than in Jurkat cell line （ P 〈 0.05 ）. Conclusion： The high expression of CCR7 in T-cell lymphoma is related to the invasion of tumors. CCR7 may promote tumor invasion and metastasis through the PI3K/Akt signal pathways.