Interleukin-22 Mediates the Chemotactic Migration of Breast Cancer Cells and Macrophage Infiltration of the Bone Microenvironment by Potentiating S1P/SIPR Signaling

被引:21
作者
Kim, Eun-Young [1 ,2 ]
Choi, Bongkun [1 ,2 ]
Kim, Ji-Eun [1 ,2 ]
Park, Si-On [1 ,2 ]
Kim, Sang-Min [1 ]
Chang, Eun-Ju [1 ,2 ,3 ]
机构
[1] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Biomed Sci, Seoul 05505, South Korea
[2] Univ Ulsan, Coll Med, Asan Med Ctr, Stem Cell Immunomodulat Res Ctr, Seoul 05505, South Korea
[3] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Biochem & Mol Biol, Seoul 05505, South Korea
基金
新加坡国家研究基金会;
关键词
interleukin; 22; breast cancer; IL22R1; S1P; S1PR1; metastasis; SPHINGOSINE 1-PHOSPHATE RECEPTORS; LUNG-CANCER; KINASE; EXPRESSION; SPHINGOSINE-1-PHOSPHATE; IL-22; PROLIFERATION; PROGRESSION; RESISTANCE; INVASION;
D O I
10.3390/cells9010131
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The interleukin-22 (IL-22) signaling pathway is well known to be involved in the progression of various cancer types but its role in bone metastatic breast cancer remains unclear. We demonstrate using human GEO profiling that bone metastatic breast cancer displays elevated interleukin-22 receptor 1 (IL-22R1) and sphingosine-1-phosphate receptor 1 (S1PR1) expression. Importantly, IL-22 stimuli promoted the expression of IL-22R1 and S1PR1 in aggressive MDA-MB-231 breast cancer cells. IL-22 treatment also increased sphingosine-1-phosphate production in mesenchymal stem cells (MSCs) and induced the sphingosine-1-phosphate (S1P)-mediated chemotactic migration of MDA-MB-231 cells. This effect was inhibited by an S1P antagonist. In addition to the S1PR1 axis, IL-22 stimulated the expression of matrix metalloproteinase-9 (MMP-9), thereby promoting breast cancer cell invasion. Moreover, IL-22 induced IL22R1 and S1PR1 expression in macrophages, myeloid cell, and MCP1 expression in MSCs to facilitate macrophage infiltration. Immunohistochemistry indicated that IL-22R1 and S1PR1 are overexpressed in invasive malignant breast cancers and that this correlates with the MMP-9 levels. Collectively, our present results indicate a potential role of IL-22 in driving the metastasis of breast cancers into the bone microenvironment through the IL22R1-S1PR1 axis.
引用
收藏
页数:17
相关论文
共 44 条
  • [1] Plasma Sphingolipids and Lung Cancer: A Population-Based, Nested Case-Control Study
    Alberg, Anthony J.
    Armeson, Kent
    Pierce, Jason S.
    Bielawski, Jacek
    Bielawska, Alicja
    Visvanathan, Kala
    Hill, Elizabeth G.
    Ogretmen, Besim
    [J]. CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2013, 22 (08) : 1374 - 1382
  • [2] The Role of Sphingosine-1-Phosphate in Breast Cancer Tumor-Induced Lymphangiogenesis
    Aoyagi, Tomoyoshi
    Nagahashi, Masayuki
    Yamada, Akimitsu
    Takabe, Kazuaki
    [J]. LYMPHATIC RESEARCH AND BIOLOGY, 2012, 10 (03) : 97 - 106
  • [3] Aberrant expression of IL-22 receptor 1 and autocrine IL-22 stimulation contribute to tumorigenicity in ALK+ anaplastic large cell lymphoma
    Bard, J. Dien
    Gelebart, P.
    Anand, M.
    Amin, H. M.
    Lai, R.
    [J]. LEUKEMIA, 2008, 22 (08) : 1595 - 1603
  • [4] Sphingosine 1-phosphate receptors in health and disease: Mechanistic insights from gene deletion studies and reverse pharmacology
    Brinkmann, Volker
    [J]. PHARMACOLOGY & THERAPEUTICS, 2007, 115 (01) : 84 - 105
  • [5] Osteoblast-derived sphingosine 1-phosphate to induce proliferation and confer resistance to therapeutics to bone metastasis-derived prostate cancer cells
    Brizuela, Leyre
    Martin, Claire
    Jeannot, Pauline
    Ader, Isabelle
    Gstalder, Cecile
    Andrieu, Guillaume
    Bocquet, Magalie
    Laffosse, Jean-Michel
    Gomez-Brouchet, Anne
    Malavaud, Bernard
    Sabbadini, Roger A.
    Cuvillier, Olivier
    [J]. MOLECULAR ONCOLOGY, 2014, 8 (07) : 1181 - 1195
  • [6] Choi B, 2015, ANTICANCER RES, V35, P2663
  • [7] Sphingosine 1-phosphate: A Potential Molecular Target for Ovarian Cancer Therapy?
    Dai, Lan
    Xia, Pu
    Di, Wen
    [J]. CANCER INVESTIGATION, 2014, 32 (03) : 71 - 80
  • [8] De Miguel MP, 2012, CURR MOL MED, V12, P574
  • [9] Metabolic crosstalk in the breast cancer microenvironment
    Dias, Ana S.
    Almeida, Catarina R.
    Helguero, Luisa A.
    Duarte, Iola F.
    [J]. EUROPEAN JOURNAL OF CANCER, 2019, 121 : 154 - 171
  • [10] Mesenchymal Stromal Cells: Emerging Roles in Bone Metastasis
    Graham, Nicola
    Qian, Bin-Zhi
    [J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2018, 19 (04)