DOI QR코드

DOI QR Code

Enhanced macrophage uptake of radiolabeled liposome triggered by ginseng extracts

  • Lee, Woonghee (Department of Molecular Medicine, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University) ;
  • Rhee, Man Hee (College of Veterinary Medicine and Stem Cell Research Therapeutic Institute, Kyungpook National University) ;
  • Yoo, Jeongsoo (Department of Molecular Medicine, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University)
  • Received : 2019.12.12
  • Accepted : 2019.12.28
  • Published : 2019.12.30

Abstract

During tumor progression various immunosuppressive cells are recruited to a tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are particularly abundant in TME. Based on their function, macrophages are categorized into two phenotypes: tumoricidal M1 and tumor-supportive M2. Generally, TAMs closely resemble M2-macrophages and lead to tumor growth. However, their phenotype can be changed by immune activator from M2 to M1 and thus promote tumor immunotherapy. Ginseng extracts are well known for its anti-tumor and anti-inflammatory effects from numerous reported studies. However, the mechanism of their effects is still not clear. Recently, some studies suggested that ginseng extracts induced immune activation as well as anti-tumor activities by a repolarization of activated macrophage from M2 phenotype to M1 phenotype. But, further verification about the mechanism as to how ginseng extracts can stimulate the immune response is still needed. In this study, we investigated whether ginseng extracts can alter the phenotype from M2 macrophages to M1 macrophages in mice by using a radiolabeled liposome. And we also evaluated the potential of radiolabeled liposome as a nuclear imaging agent to monitor the transition of phenotype of TAMs. In conclusion, the ginseng extracts seem to change the phenotype of macrophages from M2 to M1 like as lipopolysaccharide (LPS) in mice.

Acknowledgement

Supported by : 한국연구재단

References

  1. Mbeunkui F, Johann DJ, Jr. Cancer and the tumor microenvironment: a review of an essential relationship. Cancer Chemother Pharmacol 2009;63:571-582. https://doi.org/10.1007/s00280-008-0881-9
  2. Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med 2013;19:1423-1437. https://doi.org/10.1038/nm.3394
  3. Joyce JA. Therapeutic targeting of the tumor microenvironment. Cancer Cell 2005;7:513-520. https://doi.org/10.1016/j.ccr.2005.05.024
  4. Hembruff SL, Cheng N. Chemokine signaling in cancer: Implications on the tumor microenvironment and therapeutic targeting. Cancer Ther 2009;7:254-267.
  5. Noy R, Pollard JW. Tumor-associated macrophages: from mechanisms to therapy. Immunity 2014;41:49-61. https://doi.org/10.1016/j.immuni.2014.06.010
  6. Chen Y, Song Y, Du W, Gong L, Chang H, Zou Z. Tumorassociated macrophages: an accomplice in solid tumor progression. J Biomed Sci 2019;26:78. https://doi.org/10.1186/s12929-019-0568-z
  7. Chanmee T, Ontong P, Konno K, Itano N. Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment. Cancers 2014;6:1670-1690. https://doi.org/10.3390/cancers6031670
  8. Brune B, Weigert A, Dehne N. Macrophage Polarization In The Tumor Microenvironment. Redox Biol 2015;5:419.
  9. Dehne N, Mora J, Namgaladze D, Weigert A, Brune B. Cancer cell and macrophage cross-talk in the tumor microenvironment. Curr Opin Pharmacol 2017;35:12-19. https://doi.org/10.1016/j.coph.2017.04.007
  10. Ngambenjawong C, Gustafson HH, Pun SH. Progress in tumor-associated macrophage (TAM)-targeted therapeutics. Adv Drug Deliver Rev 2017;114:206-221. https://doi.org/10.1016/j.addr.2017.04.010
  11. Vasievich EA, Huang L. The Suppressive Tumor Microenvironment: A Challenge in Cancer Immunotherapy. Mol Pharmaceut 2011;8:635-641. https://doi.org/10.1021/mp1004228
  12. Muraoka D, Seo N, Hayashi T, Tahara Y, Fujii K, Tawara I, et al. Antigen delivery targeted to tumor-associated macrophages overcomes tumor immune resistance. J Clin Invest 2019;129:1278-1294. https://doi.org/10.1172/JCI97642
  13. Ginhoux F, Schultze JL, Murray PJ, Ochando J, Biswas SK. New insights into the multidimensional concept of macrophage ontogeny, activation and function. Nat Immunol 2016;17:34-40. https://doi.org/10.1038/ni.3324
  14. Green CE, Liu T, Montel V, Hsiao G, Lester RD, Subramaniam S, et al. Chemoattractant Signaling between Tumor Cells and Macrophages Regulates Cancer Cell Migration, Metastasis and Neovascularization. Plos One. 2009;4:e6713. https://doi.org/10.1371/journal.pone.0006713
  15. Zhang F, Parayath NN, Ene CI, Stephan SB, Koehne AL, Coon ME, et al. Genetic programming of macrophages to perform anti-tumor functions using targeted mRNA nanocarriers. Nat Commun 2019;10:3974. https://doi.org/10.1038/s41467-019-11911-5
  16. Galluzzi L, Chan TA, Kroemer G, Wolchok JD, Lopez-Soto A. The hallmarks of successful anticancer immunotherapy. Sci Transl Med 2018;10:459.
  17. Qie Y, Yuan H, von Roemeling CA, Chen Y, Liu X, Shih KD, et al. Surface modification of nanoparticles enables selective evasion of phagocytic clearance by distinct macrophage phenotypes. Sci Rep 2016;6:26269. https://doi.org/10.1038/srep26269
  18. Han S, Wang W, Wang S, Wang S, Ju R, Pan Z, et al. Multifunctional biomimetic nanoparticles loading baicalin for polarizing tumor-associated macrophages. Nanoscale 2019;11:20206-20220. https://doi.org/10.1039/C9NR03353J
  19. Hu GR, Guo MF, Xu JJ, Wul F, Fan JS, Huang Q, et al. Nanoparticles Targeting Macrophages as Potential Clinical Therapeutic Agents Against Cancer and Inflammation. Front Immunol 2019;10:1998. https://doi.org/10.3389/fimmu.2019.01998
  20. Cully M. CANCER Re-educating tumour-associated macrophages with nanoparticles. Nat Rev Drug Discov 2018;17:468. https://doi.org/10.1038/nrd.2018.102
  21. Ahuja A, Kim JH, Kim JH, Yi YS, Cho JY. Functional role of ginseng-derived compounds in cancer. J Ginseng Res 2018;42:248-254. https://doi.org/10.1016/j.jgr.2017.04.009
  22. Lee SM, Bae BS, Park HW, Ahn NG, Cho BG, Cho YL, et al. Characterization of Korean Red Ginseng (Panax ginseng Meyer): History, preparation method, and chemical composition. J Ginseng Res 2015;39:384-391. https://doi.org/10.1016/j.jgr.2015.04.009
  23. Baek KS, Yi YS, Son YJ, Jeong D, Sung NY, Aravinthan A, et al. Comparison of anticancer activities of Korean Red Ginseng-derived fractions. J Ginseng Res 2017;41:386-391. https://doi.org/10.1016/j.jgr.2016.11.001
  24. Byeon SE, Lee J, Kim JH, Yang WS, Kwak YS, Kim SY, et al. Molecular mechanism of macrophage activation by red ginseng acidic polysaccharide from Korean red ginseng. Mediators Inflamm 2012;2012:732860.
  25. Paul S, Shin HS, Kang SC. Inhibition of inflammations and macrophage activation by ginsenoside-Re isolated from Korean ginseng (Panax ginseng C.A. Meyer). Food Chem Toxicol 2012;50:1354-1361. https://doi.org/10.1016/j.fct.2012.02.035
  26. Yayeh T, Jung KH, Jeong HY, Park JH, Song YB, Kwak YS, et al. Korean Red Ginseng Saponin Fraction Downregulates Proinflammatory Mediators in LPS Stimulated RAW264.7 Cells and Protects Mice against Endotoxic Shock. J Ginseng Res 2012;36:263-269. https://doi.org/10.5142/jgr.2012.36.3.263
  27. Zhang YF, Qiu ZD, Qiu Y, Su T, Qu P, Jia AL. Functional Regulation of Ginsenosides on Myeloid Immunosuppressive Cells in the Tumor Microenvironment. Integr Cancer Ther 2019;18:1534735419886655.
  28. Cao M, Yan H, Han X, Weng L, Wei Q, Sun X, et al. Ginseng-derived nanoparticles alter macrophage polarization to inhibit melanoma growth. J Immunother Cancer 2019;7:326. https://doi.org/10.1186/s40425-019-0817-4
  29. Kim J, Pandya DN, Lee W, Park JW, Kim YJ, Kwak W, et al. Vivid tumor imaging utilizing liposome-carried bimodal radiotracer. ACS Med Chem Lett 2014;5:390-394. https://doi.org/10.1021/ml400513g
  30. Sun P, Wang H, He Z, Chen X, Wu Q, Chen W, et al. Fasting inhibits colorectal cancer growth by reducing M2 polarization of tumor-associated macrophages. Oncotarget 2017;8:74649-74660. https://doi.org/10.18632/oncotarget.20301
  31. Shi J, Kantoff PW, Wooster R, Farokhzad OC. Cancer nanomedicine: progress, challenges and opportunities. Nat Rev Cancer 2017;17:20-37. https://doi.org/10.1038/nrc.2016.108
  32. Yi PF, Bi WY, Shen HQ, Wei Q, Zhang LY, Dong HB, et al. Inhibitory effects of sulfated 20(S)-ginsenoside Rh2 on the release of pro-inflammatory mediators in LPS-induced RAW 264.7 cells. Eur J Pharmacol 2013;712:60-66. https://doi.org/10.1016/j.ejphar.2013.04.036