«Previous Article|Table of Contents|Next Article»

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:

2023 15

Page:

2782-2788

Research Field:

Publishing date:

Info

Title:

Mechanism of tumor-associated macrophage-derived exosomes promoting paclitaxel resistance of prostate cancer cells via miR-21

Author(s):

LIANG Yonggang¹; XIAO Hua¹; DONG Haibo²; XIE Linsen¹

1.Department of Laboratory Medicine,Zhengzhou Central Hospital Affiliated to Zhengzhou University,Henan Zhengzhou 450001, China;2.Department of Laboratory Medicine,Zhengzhou Yihe Hospital,Henan Zhengzhou 450018,China.

Keywords:

tumor-associated macrophages; exosomes; prostate cancer; drug resistance; paclitaxel; microRNA-21

PACS:

R737.25

DOI:

10.3969/j.issn.1672-4992.2023.15.005

Abstract:

Objective:To explore the regulatory effect of exosomes(Exos) on miR-21 and its effect on paclitaxel resistance in prostate cancer(PC) cells.Methods:Prostate cancer tissues and adjacent tissues were collected,and the positive expression of CD68,M1 macrophage surface marker(CD86),and M2 macrophage surface marker(CD206) was detected by immunohistochemistry,and then macrophage infiltration and phenotypic changes were identified.The human macrophage cell line THP-1 was used to induce the establishment of M2 macrophage polarization model,and Exos was extracted by differential centrifugation,and co-cultured with prostate cancer cells PC-3,which were set up PC-3 group,PC-3+Exos group,PC-3+Docetaxel(DTX) group,and PC-3+Exos+DTX group.Cell proliferation activity was detected by CCK-8.Cell migration ability was detected by Transwell.The expression of miR-21 in Exos and cells were detected by qRT-PCR.The levels of cell resistance proteins(P-gp,Txr1) were detected by Western blot.After knockdown the expression of miR-21 in Exos or blocking the secretion of Exos in macrophages,it was co-cultured with PC-3 and implanted subcutaneously in nude mice.After DTX intervention,tumor volume and weight were measured to verify the influences of Exos on miR-21 regulation and PC-3 drug resistance.Results:M2 macrophages were the predominant cells in PC cancer tissues.M2-type Exos had a diameter of about 100 nm and a cup-like particle shape.They were able to be taken up by PC-3 cells,and highly expressed miR-21.Compared with PC-3 group,M2-type Exos were was able to promote PC-3 cell proliferation,migration,inhibit apoptosis and promote the expression of miR-21 and drug-resistant proteins P-gp and Txr1(P＜0.05).Under DTX intervention,M2-type Exos were able to further promote the proliferation and migration of PC-3 cells,and aggravate the resistance of PC to DTX(P＜0.05).Knockdown the expression of miR-21 in Exos or blocking the secretion of Exos was able to reduce tumor volume and weight,and increase the sensitivity to DTX chemotherapy(P＜0.05).Conclusion:M2 macrophage Exos can promote the proliferation and migration of PC cells and aggravate the resistance of PC to DTX by transmitting miR-21.

References:

[1]PINHEIRO LC,SOROKA O,KERN LM,et al.Racial disparities in diabetes care among incident breast,prostate,and colorectal cancer survivors:a SEER medicare study［J］.J Cancer Surviv,2021,21(4):1-4.
[2] GALSKY MD,VOGELZANG NJ.Docetaxel-based combination therapy for castration-resistant prostate cancer［J］.Ann Oncol,2010,21(11):2135-2144.
[3] KUSHNIR I,MALLICK R,ONG M,et al.Docetaxel dose-intensity effect on overall survival in patients with metastatic castrate-sensitive prostate cancer［J］.Cancer Chemother Pharmacol,2020,85(5):863-868.
[4] SCHNEPP PM,SHELLEY G,DAI J,et al.Single-cell transcriptomics analysis identifies nuclear protein 1 as a regulator of docetaxel resistance in prostate cancer cells［J］.Mol Cancer Res,2020,18(9):1290-1301.
[5] WANG Y,XU Y,DAI X,et al.The prognostic landscape of adaptive immune resistance signatures and infiltrating immune cells in the tumor microenvironment of uveal melanoma［J］.Exp Eye Res,2020,196(1):1080-1099.
[6] RIHAWI K,RICCI AD,RIZZO A,et al.Tumor-associated macrophages and inflammatory microenvironment in gastric cancer:novel translational implications［J］.Int J Mol Sci,2021,22(8):3805-3820.
[7] BALAJI S,KIM U,MUTHUKKARUPPAN V,et al.Emerging role of tumor microenvironment derived exosomes in therapeutic resistance and metastasis through epithelial-to-mesenchymal transition［J］.Life Sci,2021,280(1):1197-1210.
[8] ZHENG P,CHEN L,YUAN X,et al.Exosomal transfer of tumor-associated macrophage-derived miR-21 confers cisplatin resistance in gastric cancer cells［J］.J Exp Clin Cancer Res,2017,36(1):53-66.
[9] 廖高源,骆华,刘琛,等.干扰miR-21调控人前列腺癌细胞株PC-3增殖、迁移及侵袭的实验研究［J］.临床和实验医学杂志,2019,18(13):1379-1383. LIAO GY,LUO H,LIU C,et al.Experimental study on regulation of proliferation,migration and invasion of human prostate cancer cell line PC-3 by miR-21［J］.J Clin Exp Med,2019,18(13):1379-1383.
[10] 郑乃盛,汪婷婷,袁向亮,等.肿瘤相关巨噬细胞来源外泌体激活IFN通路促进胃癌细胞免疫逃逸［J］.现代免疫学,2021,41(1):24-31. ZHENG NS,WANG TT,YUAN XL,et al.Tumor-associated macrophages-derived exosomes promote immune escape of gastric cancer cells via IFN pathway［J］.Current Immunol,2021,41(1):24-31.
[11] 李江涛,张静.环孢素A对前列腺癌PC-3细胞紫杉醇耐药的实验研究［J］.广西医科大学学报,2020,37(10):1804-1809. LI JT,ZHANG J.Study on the resistance of cyclosporine A to paclitaxel in prostate cancer PC-3 cells［J］.J Guangxi Med Uni,2020,37(10):1804-1809.
[12] 傅伟,游旭军,丁劲,等.扶正抑瘤方对前列腺癌荷瘤裸鼠的抑癌作用及血清IL-2表达的研究［J］.中医药导报,2018,24(23):24-27. FU W,YOU XJ,DING J,et al.Study on tumor suppressing effect of Fuzheng Yiliu Decoction on prostate cancer bearing nude mice and expression of serum IL-2［J］.Guiding J Trad Chin Med Pharmacol,2018,24(23):24-27.
[13] DONG L,MYERS KV,PIENTA KJ,et al.Understanding the tumor-immune microenvironment in prostate cancer［J］.Curr Opin Oncol,2021,33(3):231-237.
[14] MIDAVAINE E,COTE J,SARRET P,et al.The multifaceted roles of the chemokines CCL2 and CXCL12 in osteophilic metastatic cancers［J］.Cancer Metastasis Rev,2021,40(2):427-445.
[15] 吴从严，楼美清，贾玉,等.肿瘤相关巨噬细胞研究进展［J］.现代肿瘤医学，2020,28(03):508-512. WU CY,LOU MQ,JIA Y,et al.Research progression of tumor-associated macrophage［J］.Modern Oncology,2020,28(03):508-512.
[16] 陈成,谢旭,巴明臣.肿瘤相关巨噬细胞在肿瘤进展中作用的研究进展［J］.癌症进展,2021,19(11):6-12. CHEN C,XIE X,BA MC.Research progress on the role of tumor-associated macrophages in tumor progression ［J］.Cancer Prog,2021,19(11):6-12.
[17] 杨硕,杨清玲,陈昌杰,等.肿瘤微环境中外泌体在肿瘤发生发展中作用及机制［J］.分子诊断与治疗杂志,2020,12(3):396-400. YANG S,YANG QL,CHEN CJ,et al.Role and mechanism of exosomes in tumor microenvironment in tumorigenesis and development［J］.J Mol Diag Thera,2020,12(3):396-400.
[18] FANG Y,ZHOU W,RONG Y,et al.Exosomal miRNA-106b from cancer-associated fibroblast promotes gemcitabine resistance in pancreatic cancer［J］.Exp Cell Res,2019,383(1):1115-1143.
[19] AU YEUNG CL,CO NN,TSURUGA T,et al.Exosomal transfer of stroma-derived miR-21 confers paclitaxel resistance in ovarian cancer cells through targeting APAF1［J］.Nat Commun,2016,29(7):1115-1120.
[20] DANARTO R,ASTUTI I,UMBAS R,et al.Urine miR-21-5p and miR-200c-3p as potential non-invasive biomarkers in patients with prostate cancer［J］.Turk J Urol,2019,46(1):26-30.
[21] KANAGASABAI T,LI G,SHEN TH,et al.MicroRNA-21 deficiency suppresses prostate cancer progression through downregulation of the IRS1-SREBP-1 signaling pathway［J］.Cancer Lett,2022,525:46-54.
[22] 李醒,黄俊星.lncRNA MEG3作为miR-21的ceRNA在恶性肿瘤中的作用［J］.国际肿瘤学杂志,2020,47(1):35-38. LI X,HUANG JX.Role of lncRNA MEG3 as ceRNA of miR-21 in cancer［J］.J Int Oncol,2020,47(1):35-38.

Memo

Memo:

河南省医学科技攻关计划联合共建项目（编号：LHGJ20200778）

Common functions

Last Update: 2023-06-30