Department of Gynecology, Fujian Cancer Hospital, Clinical Oncology School of Fujian Medical University, Fuzhou, China.
Department of Oncological Nursing, Fujian Cancer Hospital, Clinical Oncology School of Fujian Medical University, Fuzhou, Fujian, China.
Expert Rev Clin Immunol. 2024 May;20(5):559-569. doi: 10.1080/1744666X.2024.2305808. Epub 2024 Jan 24.
This study aimed to check the expression profile of the C-X-C motif chemokine ligands (CXCLs)-C-X-C motif chemokine receptor 2 (CXCR2) axis in cervical cancer and to explore the cross-talk between cervical cancer cells and neutrophils via CXCLs-CXCR2 axis.
Available RNA-sequencing data based on bulk tissues and single-cell/nucleus RNA-sequencing data were used for bioinformatic analysis. Cervical cancer cell lines Hela and SiHa cells were utilized for in and studies.
Except for neutrophils, CXCR2 mRNA expression is limited in other types of cells in the cervical tumor microenvironment. CXCLs bind to CXCR2 and are mainly expressed by tumor cells. CXCL1, 2, 3, 5, 6, and 8, which are consistently associated with neutrophil infiltration, are also linked to poor prognosis. SB225002 (a CXCR2 inhibitor) treatment significantly impairs SiHa cell-induced neutrophil migration. CXCL1, CXCL2, CXCL5, or CXCL8 neutralized conditioned medium from SiHa cells have weaker recruiting effects. The conditioned medium of neutrophils from healthy donors can slow cancer cell proliferation. Conditioned medium of tumor-associated neutrophils (TANs) can drastically enhance cervical cancer cell growth in and .
The CXCLs-CXCR2 axis is critical in neutrophil recruitment and tumor cell proliferation in the cervical cancer microenvironment.
本研究旨在检测 C-X-C 基序趋化因子配体（CXCLs）-C-X-C 基序趋化因子受体 2（CXCR2）轴在宫颈癌中的表达谱，并通过 CXCLs-CXCR2 轴探索宫颈癌细胞与中性粒细胞之间的串扰。
使用基于批量组织的可用 RNA 测序数据和单细胞/核 RNA 测序数据进行生物信息学分析。使用宫颈癌细胞系 Hela 和 SiHa 细胞进行体内和体外研究。
除中性粒细胞外，CXCR2mRNA 在宫颈肿瘤微环境中的其他类型细胞中的表达受限。CXCLs 与 CXCR2 结合，主要由肿瘤细胞表达。与中性粒细胞浸润一致且与预后不良相关的 CXCL1、2、3、5、6 和 8 也存在关联。SB225002（CXCR2 抑制剂）处理显著损害 SiHa 细胞诱导的中性粒细胞迁移。中和 SiHa 细胞条件培养基中的 CXCL1、CXCL2、CXCL5 或 CXCL8 后，招募作用减弱。来自健康供体的中性粒细胞的条件培养基可减缓癌细胞增殖。肿瘤相关中性粒细胞（TANs）的条件培养基可在体内和体外显著增强宫颈癌细胞的生长。
在宫颈癌微环境中，CXCLs-CXCR2 轴在中性粒细胞募集和肿瘤细胞增殖中起关键作用。
