Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Department of Clinical Analysis, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.
Cytokine. 2019 Jun;118:160-167. doi: 10.1016/j.cyto.2018.03.001. Epub 2018 Mar 15.
Chemokines and chemokine receptors are critical in oral tumourigenesis. The atypical chemokine receptor ACKR2 is a scavenger of CC chemokines controlling the availability of these molecules at tumour sites, but the role of ACKR2 in the context of oral carcinogenesis is unexplored.
In this study, wild-type (WT) and ACKR2 deficient mice (ACKR2) were treated with chemical carcinogen 4-nitroquinoline-1-oxide (4NQO) for induction of oral carcinogenesis. Tongues were collected for macro and microscopic analysis and to evaluate the expression of ACKRs, CC chemokines and its receptors, inflammatory cytokines, angiogenic factors, adhesion molecules and extracellular matrix components.
An increased expression of ACKR2 in squamous cell carcinoma (SCC) lesions of 4NQO-treated WT mice was observed. No significant differences were seen in the ACKR1, ACKR3 and ACKR4 mRNA expression comparing SCC lesions from WT and ACKR2 treated mice. Significantly higher expression of CCL2, IL-6 and IL-17 was detected in ACKR2 treated mice. In contrast, the expression of other CC-chemokines, and receptors, angiogenic factors, adhesion molecules and extracellular matrix components were similarly increased in SCC lesions of both groups. Clinical and histopathological analysis revealed no differences in inflammatory cell recruitment and in the SCC incidence comparing WT and ACKR2 treated mice.
The results suggest that ACKR2 expression regulates inflammation in tumour-microenvironment but the absence of ACKR2 does not impact chemically-induced oral carcinogenesis.
趋化因子和趋化因子受体在口腔肿瘤发生中起着关键作用。非典型趋化因子受体 ACKR2 是 CC 趋化因子的清除剂，可控制肿瘤部位这些分子的可用性，但 ACKR2 在口腔癌发生中的作用尚未得到探索。
在这项研究中，野生型（WT）和 ACKR2 缺陷型（ACKR2）小鼠接受化学致癌物 4-硝基喹啉-1-氧化物（4NQO）处理以诱导口腔癌发生。收集舌头进行宏观和微观分析，并评估 ACKR、CC 趋化因子及其受体、炎症细胞因子、血管生成因子、粘附分子和细胞外基质成分的表达。
在 4NQO 处理的 WT 小鼠的鳞状细胞癌（SCC）病变中观察到 ACKR2 的表达增加。WT 和 ACKR2 处理的小鼠的 SCC 病变中，ACKR1、ACKR3 和 ACKR4 mRNA 的表达没有明显差异。在 ACKR2 处理的小鼠中，CCL2、IL-6 和 IL-17 的表达明显更高。相比之下，两组 SCC 病变中其他 CC-趋化因子、受体、血管生成因子、粘附分子和细胞外基质成分的表达也同样增加。临床和组织病理学分析显示，WT 和 ACKR2 处理的小鼠在炎症细胞募集和 SCC 发生率方面没有差异。
这些结果表明，ACKR2 表达调节肿瘤微环境中的炎症，但 ACKR2 的缺失不会影响化学诱导的口腔癌发生。
