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低氧条件下巨噬细胞分泌CCL22促进三阴乳腺癌转移

陈敏 胡绍勇 何成思 邹争志

陈敏, 胡绍勇, 何成思, 邹争志. 低氧条件下巨噬细胞分泌CCL22促进三阴乳腺癌转移[J]. 华南师范大学学报(自然科学版), 2022, 54(2): 83-89. doi: 10.6054/j.jscnun.2022030
引用本文: 陈敏, 胡绍勇, 何成思, 邹争志. 低氧条件下巨噬细胞分泌CCL22促进三阴乳腺癌转移[J]. 华南师范大学学报(自然科学版), 2022, 54(2): 83-89. doi: 10.6054/j.jscnun.2022030
CHEN Min, HU Shaoyong, HE Chengsi, ZOU Zhengzhi. Macrophages Secreting CCL22 to Promote Triple-negative Breast Cancer Metastasis Under Hypoxia[J]. Journal of South China normal University (Natural Science Edition), 2022, 54(2): 83-89. doi: 10.6054/j.jscnun.2022030
Citation: CHEN Min, HU Shaoyong, HE Chengsi, ZOU Zhengzhi. Macrophages Secreting CCL22 to Promote Triple-negative Breast Cancer Metastasis Under Hypoxia[J]. Journal of South China normal University (Natural Science Edition), 2022, 54(2): 83-89. doi: 10.6054/j.jscnun.2022030

低氧条件下巨噬细胞分泌CCL22促进三阴乳腺癌转移

doi: 10.6054/j.jscnun.2022030
基金项目: 

国家自然科学基金项目 81972479

广东省自然科学基金项目 2019A1515011100

广东省普通高校特色创新类项目 2021KTSCX026

广州市科技计划项目 201904010038

详细信息
    通讯作者:

    邹争志,Email:zouzhengzhi@m.scnu.edu.cn

  • 中图分类号: R453.9; R34

Macrophages Secreting CCL22 to Promote Triple-negative Breast Cancer Metastasis Under Hypoxia

  • 摘要: 三阴乳腺癌(Triple Negative Breast Cancer, TNBC)是乳腺癌中恶性程度最高的一种亚型,表现为很高的转移潜能。巨噬细胞,即肿瘤相关巨噬细胞(Tumor-Associated Macrophages, TAM),在促进TNBC转移中起了重要作用。乳腺癌作为一种实体肿瘤,往往处于缺氧环境中。低氧环境能够促进癌细胞的转移,然而低氧环境中巨噬细胞在促进肿瘤转移中的作用仍然不清楚。在该研究中,THP1细胞被诱导成TAM,经过缺氧培养后,通过Transwell实验检测其促进三阴乳腺癌细胞BT-549和MDA-MB-231的细胞迁移能力;通过尾静脉注射,将MDA-MB-231细胞移植于祼鼠体内,CT扫描,分析了TAM促进TNBC细胞的器官转移能力;通过ELISA实验检测低氧对TAM分泌的肿瘤转移相关因子的影响,通过GDSC在线软件分析了CCL22受体CCR4和其他CCR在乳腺癌组织与正常组织中表达的差异。结果表明低氧条件下巨噬细胞通过分泌CCL22的表达来促进三阴乳腺癌细胞迁移:经过缺氧培养后的TAM显著增强了TNBC细胞迁移能力,以及促进癌细胞在体内向肺转移;低氧诱导TAM分泌CCL22;CCL22受体CCR4在乳腺癌组织中的表达显著高于在正常组织中的。
  • 图  1  3种CM处理的三阴乳腺癌细胞Transwell实验

    注:M0代表M0巨噬细胞,TAM代表肿瘤相关巨噬细胞,Hyp代表低氧(hypoxia);数据表示为x±s;* * *表示P<0.001。

    Figure  1.  The Transwell-detected cell migration of TNBC treated with three CM

    图  2  RT-PCR检测3种CM处理的MDA-MB-231细胞迁移相关基因表达

    注:M0代表M0巨噬细胞,TAM代表肿瘤相关巨噬细胞,Hyp代表低氧(hypoxia);数据表示为x±s;* * *表示P<0.001。

    Figure  2.  The RT-PCR-detected expression of migration-associated gene in MDA-MB-231 cells treated with three CM

    图  3  CT扫描检测三阴乳腺癌细胞肺转移灶

    注:红色箭头代表转移灶;TAM代表肿瘤相关巨噬细胞,Hyp代表低氧(hypoxia);数据表示为x±s;* *表示P<0.01,n=5。

    Figure  3.  The CT-detected TNBC lung metastasis

    图  4  通过ELISA方法检测巨噬细胞分泌细胞因子的质量浓度

    注: TAM代表肿瘤相关巨噬细胞,Hyp代表低氧(hypoxia);数据表示为x±s;* * *表示P<0.001。

    Figure  4.  The ELISA-detected concentrations of cytokines secreted by macrophage

    图  5  不同质量浓度的CCL22诱导的三阴乳腺癌细胞Transwell实验

    注: 数据表示为x±s;*表示P<0.05,* * *表示P<0.001。

    Figure  5.  The Transwell-detected TNBC cells migration induced by CCL22 of different concentrations

    表  1  CCR家族基因在乳腺癌组织与正常组织中表达的差异与比值

    Table  1.   The expression and ratio of CCR family members in breast cancer tissue and normal tissue

    基因 正常组织表达值(N) 肿瘤组织表达值(T) T/N P
    CCR1 270 320 1.19 0.19
    CCR2 98.00 110 1.12 0.32
    CCR3 1.90 3.50 1.84 7.80×10-3
    CCR4 15.00 49.00 3.27 2.20×10-7
    CCR5 140 270 1.93 3.00×10-5
    下载: 导出CSV
  • [1] 赖丽梨, 靳焕, 段华英, 等. 巨噬细胞增强宫颈癌细胞对SN-38的抗性[J]. 华南师范大学学报(自然科学版), 2021, 53(1): 63-69. doi: 10.6054/j.jscnun.2021010

    LAI L L, JIN H, DUAN H Y, et al. Macrophage's promotion of cervical cancer cell resistance to SN-38[J]. Journal of South China Normal University(Natural Science Edition), 2021, 53(1): 63-69. doi: 10.6054/j.jscnun.2021010
    [2] 关燕清, 杨鑫华, 何丽梅, 等. TNF与IFN协同诱导癌细胞凋亡机制的研究进展[J]. 华南师范大学学报(自然科学版), 2006, 8(3): 122-126. doi: 10.3969/j.issn.1000-5463.2006.03.022

    GUAN Y Q, YANG X H, HE L M, et al. Research progress of synergic mechanisms of apoptosis induced by TNF and IFN[J]. Journal of South China Normal University(Natural Science Edition), 2006, 8(3): 122-126. doi: 10.3969/j.issn.1000-5463.2006.03.022
    [3] CHEN J Q, YAO Y D, CHANG G, et al. CCL18 from tum-or-associated macrophages promotes breast cancer metastasis via PITPNM3[J]. Cancer Cell, 2011, 19(6): 814-816. doi: 10.1016/j.ccr.2011.05.024
    [4] SU S C, LIU Q, CHEN J Q, et al. A positive feedback loop between mesenchymal-like cancer cells and macrophages is essential to breast cancer metastasis[J]. Cancer Cell, 2014, 25(5): 605-620. doi: 10.1016/j.ccr.2014.03.021
    [5] MONTAGNER M, ENZO E, FORCATO M, et al. SHARP1 suppresses breast cancer metastasis by promoting degradation of hypoxia-inducible factors[J]. Nature, 2012, 487: 380-384. doi: 10.1038/nature11207
    [6] KORBECKI J, KOJDER K, SIMIŃSKA D, et al. CC chemokines in a tumor: a review of pro-cancer and anti-cancer properties of the ligands of receptors CCR1, CCR2, CCR3, and CCR4[J]. International Journal of Molecular Sciences, 2020, 21(21): 8412-8440. doi: 10.3390/ijms21218412
    [7] TANG J M, ZHONG G S, ZHANG H B, et al. LncRNA DANCR upregulates PI3K/AKT signaling through activating serine phosphorylation of RXRA[J]. Cell Death & Disease, 2018, 9(12): 1167-1178.
    [8] SHOME R, GHOSH S S. Tweaking EMT and MDR dynamics to constrain triple-negative breast cancer invasiveness by EGFR and Wnt/β-catenin signaling regulation[J]. Cellular Oncology, 2021, 44(2): 405-422. doi: 10.1007/s13402-020-00576-8
    [9] SAXENA K, JOLLY M K, BALAMURUGAN K. Hypoxia, partial EMT and collective migration: emerging culprits in metastasis[J]. Translational Oncology, 2020, 13(11): 100845-100858. doi: 10.1016/j.tranon.2020.100845
    [10] BRANCO-PRICE C, ZHANG N, SCHNELLE M, et al. Endothelial cell HIF-1α and HIF-2α differentially regulate metastatic success[J]. Cancer Cell, 2012, 21(1): 52-65. doi: 10.1016/j.ccr.2011.11.017
    [11] CHEN Y B, SONG Y C, DU W, et al. Tumor-associated macrophages: an accomplice in solid tumor progression[J]. Journal of Biomedical Science, 2019, 26(1): 1-13. doi: 10.1186/s12929-018-0495-4
    [12] 邹争志, 聂培培, 倪艺榕, 等. 硫链丝菌素诱导非小细胞肺癌细胞自噬性死亡[J]. 激光生物学报, 2014, 23(1): 33-37. https://www.cnki.com.cn/Article/CJFDTOTAL-JGSW201401007.htm

    ZOU Z Z, NIE P P, NI Y R, et al. Thiostrepton induces autophagic cell death in non-small-cell lung cancer cells[J]. Acta Laser Biology Sinica, 2014, 23(1): 33-37. https://www.cnki.com.cn/Article/CJFDTOTAL-JGSW201401007.htm
    [13] TU D Y, DOU J, WANG M K, et al. M2 macrophages contribute to cell proliferation and migration of breast cancer[J]. Cell Biology International, 2020, 45(4): 831-838.
    [14] ALLEN S G, CHEN Y C, MADDEN J M, et al. Macrophages enhance migration in inflammatory breast cancer cells via RhoC GTPase signaling[J]. Scientific Reports, 2016, 6(1): 39190-39200. doi: 10.1038/srep39190
    [15] SEMENZA G L. Molecular mechanisms mediating metastasis of hypoxic breast cancer cells[J]. Trends in Molecular Medicine, 2012, 18(9): 534-543.
    [16] QIAO J H, CHEN Y B, MI Y J, et al. Macrophages confer resistance to BET inhibition in triple-negative breast cancer by upregulating IKBKE[J]. Biochemical Pharmacology, 2020, 180: 114-126.
    [17] ARAUJO-PIRES A C, VIEIRA A E, FRANCISCONI C F, et al. IL-4/CCL22/CCR4 axis controls regulatory T-cell migration that suppresses inflammatory bone loss in murine experimental periodontitis[J]. Journal of Bone and Mineral Research, 2015, 30(3): 412-422.
    [18] YANG X X, BAO M C, FANG Y, et al. STAT3/HIF-1α signaling activation mediates peritoneal fibrosis induced by high glucose[J]. Journal of Translational Medicine, 2021, 19(1): 283-297.
    [19] NICOLAY J P, ALBRECHT J D, ALBERTI-VIOLETTI S, et al. CCR4 in cutaneous T-cell lymphoma: therapeutic targeting of a pathogenic driver[J]. European Journal of Immunology, 2021, 51(7): 1660-1671.
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出版历程
  • 收稿日期:  2021-09-19
  • 网络出版日期:  2022-05-12
  • 刊出日期:  2022-04-25

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