Human amniotic epithelial cells exert anti-cancer effects through secretion of immunomodulatory small extracellular vesicles (sEV)

被引:7
作者
Bolouri, Mohammad-Reza [1 ,6 ]
Ghods, Roya [2 ,3 ]
Zarnani, Kayhan [4 ]
Vafaei, Sedigheh [5 ]
Falak, Reza [1 ,6 ]
Zarnani, Amir-Hassan [4 ,5 ,6 ]
机构
[1] Iran Univ Med Sci, Dept Immunol, Tehran, Iran
[2] Iran Univ Med Sci, Oncopathol Res Ctr, Tehran, Iran
[3] Iran Univ Med Sci, Fac Adv Technol Med, Dept Mol Med, Tehran, Iran
[4] Univ Tehran Med Sci, Sch Publ Hlth, Dept Immunol, Tehran 1417613151, Iran
[5] ACECR, Avicenna Res Inst, Biotechnol Res Ctr, Tehran, Iran
[6] Iran Univ Med Sci, Immunol Res Ctr, Tehran 1449614535, Iran
关键词
Stem cells; Human amniotic epithelial cell; Cancer; Small extracellular vesicles (sEV); Cytotoxic T lymphocyte; Warburg's effect; Metabolomics; EMBRYONIC STEM-CELLS; EFFECTIVE ANTITUMOR IMMUNITY; DENDRITIC CELLS; CANCER-CELLS; LUNG-CANCER; EXOSOMES; MEMBRANE; BREAST; MICE; VACCINATION;
D O I
10.1186/s12935-022-02755-z
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
We identified here mechanism by which hAECs exert their anti-cancer effects. We showed that vaccination with live hAEC conferred effective protection against murine colon cancer and melanoma but not against breast cancer in an orthotopic cancer cell inoculation model. hAEC induced strong cross-reactive antibody response to CT26 cells, but not against B16F10 and 4T1 cells. Neither heterotopic injection of tumor cells in AEC-vaccinated mice nor vaccination with hAEC lysate conferred protection against melanoma or colon cancer. Nano-sized AEC-derived small-extracellular vesicles (sEV) (AD-sEV) induced apoptosis in CT26 cells and inhibited their proliferation. Co-administration of AD-sEV with tumor cells substantially inhibited tumor development and increased CTL responses in vaccinated mice. AD-sEV triggered the Warburg's effect leading to Arginine consumption and cancer cell apoptosis. Our results clearly showed that it is AD-sEV but not the cross-reactive immune responses against tumor cells that mediate inhibitory effects of hAEC on cancer development. Our results highlight the potential anti-cancer effects of extracellular vesicles derived from hAEC.
引用
收藏
页数:18
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