Extracellular Vesicles Secreted from Cancer Cell Lines Stimulate Secretion of MMP-9, IL-6, TGF-β1 and EMMPRIN

被引:35
|
作者
Redzic, Jasmina S. [1 ]
Kendrick, Agnieszka A. [1 ]
Bahmed, Karim [1 ]
Dahl, Kristin D. [2 ]
Pearson, Chad G. [2 ]
Robinson, William A. [3 ]
Robinson, Steven E. [3 ]
Graner, Michael W. [4 ]
Eisenmesser, Elan Z. [1 ]
机构
[1] Univ Colorado Denver, Sch Med, Dept Biochem & Mol Genet, Aurora, CO USA
[2] Univ Colorado Denver, Sch Med, Dept Cell & Dev Biol, Aurora, CO USA
[3] Univ Colorado Denver, Sch Med, Div Med Oncol, Aurora, CO USA
[4] Univ Colorado Denver, Sch Med, Dept Neurosurg, Aurora, CO USA
来源
PLOS ONE | 2013年 / 8卷 / 08期
关键词
MATRIX METALLOPROTEINASES; RELEASED EXOSOMES; DENDRITIC CELLS; TUMOR EXOSOMES; MICROVESICLES; PROGRESSION; COMMUNICATION; MECHANISM; METASTASIS; EXPRESSION;
D O I
10.1371/journal.pone.0071225
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Extracellular vesicles (EVs) are key contributors to cancer where they play an integral role in cell-cell communication and transfer pro-oncogenic molecules to recipient cells thereby conferring a cancerous phenotype. Here, we purified EVs using straightforward biochemical approaches from multiple cancer cell lines and subsequently characterized these EVs via multiple biochemical and biophysical methods. In addition, we used fluorescence microscopy to directly show internalization of EVs into the recipient cells within a few minutes upon addition of EVs to recipient cells. We confirmed that the transmembrane protein EMMPRIN, postulated to be a marker of EVs, was indeed secreted from all cell lines studied here. We evaluated the response to EV stimulation in several different types of recipient cells lines and measured the ability of these purified EVs to induce secretion of several factors highly upregulated in human cancers. Our data indicate that purified EVs preferentially stimulate secretion of several proteins implicated in driving cancer in monocytic cells but only harbor limited activity in epithelial cells. Specifically, we show that EVs are potent stimulators of MMP-9, IL-6, TGF-beta 1 and induce the secretion of extracellular EMMPRIN, which all play a role in driving immune evasion, invasion and inflammation in the tumor microenvironment. Thus, by using a comprehensive approach that includes biochemical, biological, and spectroscopic methods, we have begun to elucidate the stimulatory roles.
引用
收藏
页数:9
相关论文
共 50 条
  • [1] IL-6 AND MMP-9 IN SMALL CELL LUNG CANCER PATIENTS
    Kulpa, J. K.
    Wojcik, E.
    Sas-Korczynska, B.
    Walasek, T.
    [J]. TUMOR BIOLOGY, 2010, 31 : S86 - S87
  • [2] Endothelial Cells Enhance Prostate Cancer Metastasis via IL-6 → Androgen Receptor → TGF-β → MMP-9 Signals
    Wang, Xiaohai
    Lee, Soo Ok
    Xia, Shujie
    Jiang, Qi
    Luo, Jie
    Li, Lei
    Yeh, Shuyuan
    Chang, Chawnshang
    [J]. MOLECULAR CANCER THERAPEUTICS, 2013, 12 (06) : 1026 - 1037
  • [3] Multiple Myeloma Derived Extracellular Vesicle Uptake by Monocyte Cells Stimulates IL-6 and MMP-9 Secretion and Promotes Cancer Cell Migration and Proliferation
    Sheridan, Rebecca
    Brennan, Kieran
    Bazou, Despina
    O'Gorman, Peter
    Matallanas, David
    Mc Gee, Margaret M.
    [J]. CANCERS, 2024, 16 (05)
  • [4] Serum Levels of IL-1β, IL-6, TGF-β, and MMP-9 in Patients Undergoing Carotid Artery Stenting and Regulation of MMP-9 in a New In Vitro Model of THP-1 Cells Activated by Stenting
    Zhang, Rongrong
    Jiang, Fan
    Chen, Cindy Si
    Wang, Tianzhu
    Feng, Jinzhou
    Tao, Tao
    Qin, Xinyue
    [J]. MEDIATORS OF INFLAMMATION, 2015, 2015
  • [5] Role of slug in TGF-β1 mediated MMP-9 expression in human oral squamous cell cancer
    Joseph, M. J.
    Ananthanarayanan, V.
    Diamond, M. E.
    Sun, L.
    Munshi, H. G.
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (18)
  • [6] 2型糖尿病干眼症患者泪液IL-6、MMP-9、TGF-β1表达及其临床意义
    王士云
    成雅
    武传红
    张娟
    高海霞
    [J]. 现代生物医学进展, 2024, 24 (09) : 1672 - 1677
  • [9] Correlation analysis of TGF-β1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α in refractory chronic rhinosinusitis: A retrospective study
    Wen, Wulin
    Zhu, Simin
    Ma, Ruixia
    Wang, Lixin
    Shen, Xueliang
    Li, Yongchun
    Feng, Ningyu
    Wang, Le
    Liu, Ming
    Xie, Lina
    Zhang, Xueqiang
    [J]. ALLERGOLOGIA ET IMMUNOPATHOLOGIA, 2022, 50 (04) : 137 - 142
  • [10] Breast cancer cells induce stromal fibroblasts to express MMP-9 via secretion of TNF-α and TGF-β
    Stuelten, CH
    Byfield, SD
    Arany, PR
    Karpova, TS
    Stetler-Stevenson, WG
    Roberts, AB
    [J]. JOURNAL OF CELL SCIENCE, 2005, 118 (10) : 2143 - 2153