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

来源：

CANCER CELL INTERNATIONAL | 2022年 / 22卷 / 01期

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

页数：18

共 76 条

[1]

CAT-1-Mediated Arginine Uptake and Regulation of Nitric Oxide Synthases for the Survival of Human Breast Cancer Cell Lines [J].

Abdelmagid, Salma A. ;

Rickard, Jenaya A. ;

McDonald, William J. ;

Thomas, Lynn N. ;

Too, Catherine K. L. .

JOURNAL OF CELLULAR BIOCHEMISTRY, 2011, 112 (04) :1084-1092

[2]

The Human Amnion Epithelial Cell Secretome Decreases Hepatic Fibrosis in Mice with Chronic Liver Fibrosis [J].

Alhomrani, Majid ;

Correia, Jeanne ;

Zavou, Marcus ;

Leaw, Bryan ;

Kuk, Nathan ;

Xu, Rong ;

Saad, Mohamed I. ;

Hodge, Alexander ;

Greening, David W. ;

Lim, Rebecca ;

Sievert, William .

FRONTIERS IN PHARMACOLOGY, 2017, 8

[3]

BENDICH A, 1973, J IMMUNOL, V111, P284

[4]

Human amniotic epithelial cells inhibit growth of epithelial ovarian cancer cells via TGF-β1-mediated cell cycle arrest [J].

Bu, Shixia ;

Zhang, Qiuwan ;

Wang, Qian ;

Lai, Dongmei .

INTERNATIONAL JOURNAL OF ONCOLOGY, 2017, 51 (05) :1405-1414

[5]

Enhanced T-cell immunity induced by dendritic cells with phagocytosis of heat shock protein 70 gene-transfected tumor cells in early phase of apoptosis [J].

Chan, T. ;

Chen, Z. ;

Hao, S. ;

Xu, S. ;

Yuan, J. ;

Saxena, A. ;

Qureshi, M. ;

Zheng, C. ;

Xiang, J. .

CANCER GENE THERAPY, 2007, 14 (04) :409-420

[6]

Efficient antitumor immunity derived from maturation of dendritic cells that had phagocytosed apoptotic/necrotic tumor cells [J].

Chen, Z ;

Moyana, T ;

Saxena, A ;

Warrington, R ;

Jia, ZC ;

Xiang, J .

INTERNATIONAL JOURNAL OF CANCER, 2001, 93 (04) :539-548

[7]

Exploring the links between cancer and placenta development [J].

Costanzo, Vincenzo ;

Bardelli, Alberto ;

Siena, Salvatore ;

Abrignani, Sergio .

OPEN BIOLOGY, 2018, 8 (06)

[8]

Conditioned medium derived from rat amniotic epithelial cells confers protection against inflammation, cancer, and senescence [J].

Di Germanio, Clara ;

Bernier, Michel ;

Petr, Michael ;

Mattioli, Mauro ;

Barboni, Barbara ;

de Cabo, Rafael .

ONCOTARGET, 2016, 7 (26) :39051-39064

[9]

On the origin of amniotic stem cells: of mice and men [J].

Dobreva, Mariya P. ;

Pereira, Paulo N. G. ;

Deprest, Jan ;

Zwijsen, An .

INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY, 2010, 54 (05) :761-777

[10]

Antitumor Effect of Embryonic Stem Cells in a Non-Small Cell Lung Cancer Model: Antitumor Factors and Immune Responses [J].

Dong, Wei ;

Qiu, Chen ;

Shen, Hongchang ;

Liu, Qi ;

Du, Jiajun .

INTERNATIONAL JOURNAL OF MEDICAL SCIENCES, 2013, 10 (10) :1314-1320

← 1 2 3 4 5 6 7 8 →