PILRB通过影响CCL2及CCL5细胞因子分泌促进前列腺癌进展的作用与机制研究

doi:10.3969/j.issn.1006-7795.2026.02.014

首都医科大学学报 ›› 2026, Vol. 47 ›› Issue (2): 326-337.doi: 10.3969/j.issn.1006-7795.2026.02.014

PILRB通过影响CCL2及CCL5细胞因子分泌促进前列腺癌进展的作用与机制研究

吕苏展,邹凡,张镱山,王明东,全勇俊,平浩^*

首都医科大学附属北京同仁医院泌尿外科，北京 100176

收稿日期:2025-12-16 修回日期:2026-03-01 出版日期:2026-04-21 发布日期:2026-04-21
通讯作者: 平浩 E-mail:pinghaotrh@ccmu.edu.cn
基金资助:
国家自然科学基金（82573601），首都卫生发展科研专项（2024-2-2059）。

The role and mechanism of PILRB in promoting prostate cancer progression by regulating CCL2 and CCL5 secretion

Lü Suzhan， Zou Fan， Zhang Yishan， Wang Mingdong， Quan Yongjun， Ping Hao^*

Department of Urology，Beijing Tongren Hospital，Capital Medical University，Beijing 100176, China

Received:2025-12-16 Revised:2026-03-01 Online:2026-04-21 Published:2026-04-21
Supported by:
This study was supported by National Natural Science Foundation of China（82573601），Capital's Funds for Health Improvement and Research（2024-2-2059）.

摘要/Abstract

摘要： 目的研究配对免疫球蛋白样2型受体β（paired immunoglobin like type 2 receptor beta, PILRB）在前列腺癌中的表达情况和对前列腺肿瘤细胞增殖迁移和侵袭功能的影响及相关机制。方法在前列腺癌细胞中使用siRNA（small interfering RNA, siRNA）干扰PILRB表达，应用实时荧光定量聚合酶链反应（quantitative real-time polymerase chain reaction, qRT-PCR）信使RNA（messenger RNA, mRNA）表达水平。免疫组化染色和蛋白质印迹（Western blotting, WB）检测PILRB及相关蛋白的表达情况。细胞计数试剂盒8（cell counting kit-8, CCK8）、平板划痕、免疫荧光和Transwell实验检测前列腺癌细胞在体外实验中的增殖、迁移和侵袭能力。使用免疫缺陷裸鼠探究PILRB在动物体内的促癌作用。结果 PILRB在高Gleason评分的前列腺癌组织中蛋白表达水平显著高于低Gleason评分的前列腺癌组织。CCK8增殖实验、平板划痕实验与Transwell侵袭实验共同提示干扰PILRB会明显抑制前列腺癌细胞的增殖（22RV1：1.054±0.054 vs 1.959±0.032，t=40.574，P＜0.001；PC3：1.606±0.535 vs 2.178±0.479，t=22.497，P＜0.01；DU145：1.290±0.184 vs 2.147±0.597，t=38.750，P＜0.01）、侵袭(单位:个／视野)（siPILRB-2：11.500±3.271 vs 101.667±12.909，t=16.584，P＜0.001）、迁移（siPILRB-2：67.125±1.178 vs 81.588±1.454，t=21.855，P＜0.001；si-CCL2：63.100±3.019 vs 81.588±1.454，t=15.602，P＜0.001）。酶联免疫吸附实验（enzyme linked immunosorbent assay, ELISA）结果表明干扰PILRB能抑制癌细胞分泌C-C基序趋化因子配体2（C-C motif chemokine ligand 2, CCL2）、C-C基序趋化因子配体5（C-C motif chemokine ligand 5, CCL5）(pg/mL)（CCL2：82.450±3.075 vs 92.061±4.925，t=4.966，P＜0.01；CCL5：796.558±11.606 vs 816.300±19.965，t=2.564，P＜0.05；CSF-1：92.771±5.276 vs 106.787±10.016，t=3.714，P＜0.05）。同时WB结果显示siPILRB-2组CCL2蛋白相对表达量显著低于si-Control组（PILRB：0.305±0.007 vs 0.706±0.016，t=54.668，P＜0.05；CCL2：0.149±0.005 vs 0.522±0.204，t=43.221，P＜0.05），siPILRB-2组CCL5蛋白浓度略低于si-Control组（CCL5：0.204±0.005 vs 0.220±0.014，t=2.468，P＜0.05）。在体内实验中，干扰PILRB的裸鼠皮下移植瘤体积（mm3）明显更小（shPILRB：585.920±117.582 vs 1 314.462±234.633，t=6.207，P＜0.001）。结论 PILRB表达在前列腺癌细胞中明显升高，通过促进前列腺癌细胞中CCL2、CCL5的分泌，调控单核细胞与巨噬细胞向M2型分化，最终促进前列腺癌细胞的进展，PILRB有可能成为抑制前列腺癌进展的潜在治疗靶点。

关键词: 前列腺癌, PILRB, CCL2, CCL5, 增殖迁移, 免疫组化, 体内实验

Abstract: Objective To investigate the expression of paired immunoglobin like type 2 receptor beta (PILRB) in prostate cancer (PCa), and to evaluate its effects on the proliferation, migration, as well as the underlying mechanisms. Methods Small interfering RNA (siRNA) was used to knock down PILRB expression in prostate cancer cells. Quantitative real-time polymerase chain reaction (qPCR) was performed to verify the mRNA expression level. Immunohistochemistry (IHC) staining and Western blotting(WB) were employed to detect the expression of PILRB and related proteins. Cell counting kit-8 (CCK-8) assay, scratch wound healing assay, immunofluorescent staining (IF) and Transwell chamber assay were conducted to assess the proliferation, migration, and invasion capabilities of prostate cancer cells in vitro. The tumor-promoting role of PILRB in vivo was investigated using immunodeficient nude mice. Results PILRB protein expression was notably elevated in PCa tissues exhibiting high Gleason scores relative to those with low scores. Suppression of PILRB expression markedly inhibited the proliferation （22RV1：1.054±0.054 vs 1.959±0.032，t=40.574，P＜0.001；PC3：1.606±0.535 vs 2.178±0.479，t=22.497，P＜0.01；DU145：1.290±0.184 vs 2.147±0.597，t=38.750，P＜0.01）, transwell invasion assay (unit：n per field) （siPILRB-2：11.500±3.271 vs 101.667±12.909，t=16.584，P＜0.001） and migration （siPILRB-2：67.125±1.178 vs 81.588±1.454，t=21.855，P＜0.001；si-CCL2：63.100±3.019 vs 81.588±1.454，t=15.602，P＜0.001） of prostate cancer cells in vitro. Knockdown of PILRB effectively suppressed the secretion of C-C motif chemokine ligand 2 (CCL2） and C-C motif chemokine ligand 5 (CCL5） (pg/mL), as determined by ELISA （CCL2：82.450±3.075 vs 92.061±4.925，t=4.966，P＜0.01；CCL5：796.558±11.606 vs 816.300±19.965，t=2.564，P＜0.05；CSF-1：92.771±5.276 vs 106.787±10.016，t=3.714，P＜0.05）. This finding was further supported at the intracellular relative protein expression level by WB, which showed a significant downregulation of CCL2 （PILRB：0.305±0.007 vs 0.706±0.016，t=54.668，P＜0.05；CCL2：0.149±0.005 vs 0.522±0.204，t=43.221，P＜0.05）and a modest decrease in CCL5 （CCL5：0.204±0.005 vs 0.220±0.014，t=2.468，P＜0.05）in siPILRB-2-transfected cells relative to the si-Control. Subcutaneous xenograft tumors formed from PILRB-knockdown cells displayed significantly reduced tumor volumes in vivo （shPILRB：585.920±117.582 vs.1 314.462±234.633，t=6.207，P＜0.001）. Conclusion Elevated expression of PILRB in prostate cancer cells promotes the progression of prostate cancer by enhancing the secretion of CCL2 and CCL5, which modulates the differentiation of monocytes and macrophages towards the M2 phenotype. Therefore, PILRB may serve as a potential therapeutic target for suppressing prostate cancer progression.

Key words: prostate cancer, PILRB, CCL2, CCL5, proliferation and migration, immunohistochemistry, in vivo

中图分类号:

R737.25

吕苏展, 邹凡, 张镱山, 王明东, 全勇俊, 平浩. PILRB通过影响CCL2及CCL5细胞因子分泌促进前列腺癌进展的作用与机制研究[J]. 首都医科大学学报, 2026, 47(2): 326-337.

Lü Suzhan, Zou Fan, Zhang Yishan, Wang Mingdong, Quan Yongjun, Ping Hao. The role and mechanism of PILRB in promoting prostate cancer progression by regulating CCL2 and CCL5 secretion[J]. Journal of Capital Medical University, 2026, 47(2): 326-337.

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PILRB通过影响CCL2及CCL5细胞因子分泌促进前列腺癌进展的作用与机制研究

The role and mechanism of PILRB in promoting prostate cancer progression by regulating CCL2 and CCL5 secretion

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