Uptake Characterization of Tumor Cell-derived Exosomes by Natural Killer Cells
Abstract
Background: Cancer is the leading cause of death in human disease and is a major public health problem around the world. Exosomes are a promising cancer biomarker and therapy target. Recent evidence demonstrate that tumor cells could inhibit natural killer (NK) cells’ immune surveillance function by releasing exosomes into tumor microenvironment. The intercelluar uptake of tumor cell-derived exosomes by NK cells is vital for using these exosomes in tumor diagnose and therapy. We aimed to investigate the efficiency of NK cell uptake of tumor exosomes.
Methods: Exosomes derived from different tumor cells, RAW264.7 cells and NK cells were labeled by fluorescent dye and co-cultured with NK cells. The uptake rates of NK cells were observed by fluorescence microscope and analyzed by flow cytometry.
Results: NK cells could take up more exosomes from themselves and cell lines originating from bone marrow. Epithelial cell lines can take up more exosomes from epithelial cells. There was no significant difference in uptake efficiency between Jurkat cells and RAW264.7 cells by NK cells, indicating that maybe the origin other than species affects the efficiency of recipient cell uptake of exosomes. Different tumor cells derived exosomes had different uptake efficiency by NK cells.
Conclusion: There is certain pattern of NK cells uptake tumor exosomes, which provide important insights on how tumors affect NK cells and develop appropriate countermeasures. In addition, it can be also helpful to select and design proper exosomes as a drug carrier in future.
Ward EM, Flowers CR, Gansler T, et al. (2017). The importance of immunization in cancer prevention, treatment, and survivorship. CA-Cancer J Clin, 67(5): 398-410.
Xiao D, Barry S, Kmetz D, et al. (2016). Melanoma cell-derived exosomes promote epithelial-mesenchymal transition in primary melanocytes through paracrine/autocrine signaling in the tumor microenvironment. Cancer Lett, 376(2): 318-27.
Colombo M, Raposo G, Thery C (2014). Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol, 30: 255-89.
Nolte-'t Hoen E, Cremer T, Gallo RC, et al. (2016). Extracellular vesicles and viruses: Are they close relatives? Proc Natl Acad Sci U S A, 113(33): 9155-61.
Alvarez-Erviti L, Seow Y, Yin H, et al. (2011). Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol, 29(4): 341-5.
Samanta S, Rajasingh S, Drosos N, et al. (2018). Exosomes: new molecular targets of diseases. Acta Pharmacol Sin, 39(4): 501-513.
Camussi G, Deregibus MC, Bruno S, et al. (2010). Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney Int, 78(9): 838-48.
Xitong D, Xiaorong Z (2016). Targeted therapeutic delivery using engineered exosomes and its applications in cardiovascular diseases. Gene, 575(2): 377-84.
Mause SF, Weber C (2010). Microparticles: protagonists of a novel communication network for intercellular information exchange. Circ Res, 107(9): 1047-57.
Cooper MA, Fehniger TA, Caligiuri MA (2001). The biology of human natural killer-cell subsets. Trends Immunol, 22(11): 633-40.
Putz EM, Mayfosh AJ, Kos K, et al. (2017). NK cell heparanase controls tumor invasion and immune surveillance. J Clin Invest, 127(7): 2777-88.
van Ostaijen-ten Dam MM, Prins HJ, Boerman GH, et al. (2016). Preparation of Cytokine-activated NK Cells for Use in Adoptive Cell Therapy in Cancer Patients: Protocol Optimization and Therapeutic Potential. J Immunother, 39(2): 90-100.
Li Q, Ye LJ, Ren HL, et al. (2015). Multiple effects of IL-21 on human NK cells in ex vivo expansion. Immunobiology, 220(7): 876-88.
Xia Y, Zhang Q, Zhen Q, et al. (2017). Negative regulation of tumor-infiltrating NK cell in clear cell renal cell carcinoma patients through the exosomal pathway. Oncotarget, 8(23): 37783-95.
Katsiougiannis S, Chia D, Kim Y, et al. (2017). Saliva exosomes from pancreatic tumor-bearing mice modulate NK cell phenotype and antitumor cytotoxicity. Faseb J, 31(3): 998-1010.
Wen SW, Sceneay J, Lima LG, et al. (2016). The Biodistribution and Immune Suppressive Effects of Breast Cancer-Derived Exosomes. Cancer Res, 76(23): 6816-27.
Whiteside TL (2013). Immune modulation of T-cell and NK (natural killer) cell activities by TEXs (tumour-derived exosomes). Biochem Soc Trans, 41(1): 245-51.
Yao Y, Chen L, Wei W, et al. (2013). Tumor cell-derived exosome-targeted dendritic cells stimulate stronger CD8+ CTL responses and antitumor immunities. Biochem Biophys Res Commun, 436(1): 60-5.
Bu N, Wu H, Zhang G, et al. (2015). Exosomes from Dendritic Cells Loaded with Chaperone-Rich Cell Lysates Elicit a Potent T Cell Immune Response Against Intracranial Glioma in Mice. J Mol Neurosci, 56(3): 631-43.
Clayton A, Mitchell JP, Court J, et al. (2008). Human tumor-derived exosomes down-modulate NKG2D expression. J Immunol, 180(11): 7249-58.
Medina A, Ghahary A (2010). Transdifferentiated circulating monocytes release exosomes containing 14-3-3 proteins with matrix metalloproteinase-1 stimulating effect for dermal fibroblasts. Wound Repair Regen, 18(2): 245-53
Coumans FAW, Brisson AR, Buzas EI, et al. (2017). Methodological Guidelines to Study Extracellular Vesicles. Circ Res, 120(10): 1632-48.
Hoshyar N, Gray S, Han H, et al. (2016). The effect of nanoparticle size on in vivo pharmacokinetics and cellular interaction. Nanomedicine(Lond), 11(6): 673-92.
Słońska A, Cymerys J, Bańbura MW (2016). Mechanisms of endocytosis utilized by viruses during infection. Postep Hig Med Dosw (Online), 70(0): 572-80.
Zhang G, Yang P (2018). A novel cell-cell communication mechanism in the nervous system: exosomes. J Neurosci Res, 96(1): 45-52.
Caponnetto F, Manini I, Skrap M, et al. (2017). Size-dependent cellular uptake of exosomes. Nanomedicine, 13(3): 1011-20.
López-Terrada D, Cheung SW, Finegold MJ, et al. (2009). Hep G2 is a hepatoblastoma-derived cell line. Hum Pathol, 40(10): 1512-5.
Su SA, Xie Y, Fu Z, Wang Y, et al. (2017). Emerging role of exosome-mediated intercellular communication in vascular remodeling. Oncotarget,8(15): 25700-12.
| Files | ||
| Issue | Vol 47 No 6 (2018) | |
| Section | Original Article(s) | |
| Keywords | ||
| Natural killer (NK) cells Tumor cell lines Exosomes Biomarker Uptake efficiency Flow cytometry | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
