Yang Yongmei, Du Lutao, Yang Xiaoyun, Qu Ailin, Zhang Xin, Zhou Chengjun, Wang Chuanxin
Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong Province, P.R. China.
PLoS One. 2015 Mar 19;10(3):e0120059. doi: 10.1371/journal.pone.0120059. eCollection 2015.
Cellular chemotaxis is the best-known function of chemokine receptors which are closely linked with tumor metastasis. In fact, positive expression of chemokine receptors could also be identified even in some patients without metastatic tumors, while the clinical relevance of this data has not been fully established. Our studies were designed to clarify the CCR4 expression profiles and to explore its potential role in histologically node-negative (pN0) gastric cancer (GC). Immunohistochemistry (IHC) or immunohistofluorescence (IHF) analysis was performed on specimens obtained from 108 patients with pN0 GC. We found that CCR4 was aberrantly over-expressed inpN0 GC tissues, with different expression patterns on tumor cells and being associated with T-stage (P = 0.002). The matrigel in vitro invasion assay revealed that over-expression of CCR4 in GC cell lines significantly enhanced the invasive capacity of these cells. Results from real-time RT-PCR and gelatinzymography showed a significant increase in matrix metalloproteinase (MMP)-9 production induced by the forced expression of CCR4 in GC cell lines. Our data suggest that the aberrant CCR4 expression is involved in tumor invasion of pN0 GC and, conceivably, antagonists of CCR4 might be useful candidates for controlling early events in tumor progression.
细胞趋化性是趋化因子受体最为人熟知的功能，而趋化因子受体与肿瘤转移密切相关。事实上，即使在一些没有转移性肿瘤的患者中也能检测到趋化因子受体的阳性表达，然而这一数据的临床相关性尚未完全明确。我们的研究旨在阐明CCR4的表达谱，并探讨其在组织学上淋巴结阴性（pN0）的胃癌（GC）中的潜在作用。对108例pN0 GC患者的标本进行了免疫组织化学（IHC）或免疫组织荧光（IHF）分析。我们发现CCR4在pN0 GC组织中异常过度表达，在肿瘤细胞上有不同的表达模式，且与T分期相关（P = 0.002）。体外基质胶侵袭试验表明，GC细胞系中CCR4的过度表达显著增强了这些细胞的侵袭能力。实时RT-PCR和明胶酶谱分析结果显示，GC细胞系中CCR4的强制表达诱导基质金属蛋白酶（MMP）-9的产生显著增加。我们的数据表明，CCR4的异常表达参与了pN0 GC的肿瘤侵袭，可想而知，CCR4拮抗剂可能是控制肿瘤进展早期事件的有用候选药物。
