Human Tumor-Derived vs Dendritic Cell-Derived Exosomes Have Distinct Biologic Roles and Molecular Profiles

Wieckowski, Eva; Whiteside, Theresa L.

doi:10.1385/ir:36:1:247

Cited by 115 publications

(82 citation statements)

References 18 publications

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“…In vitro studies have shown MHC-II molecules enriched on the exosomes that were purified from specific APC (16,17), B7-2 enriched on the exosomes purified from DCs (18,19), TCR enriched on the exosomes purified from T cells (20,21) and CD20/BCR enriched on the exosomes purified from B cells (22). By Western blot analysis and IEM, we found there were B7-2, HLA-DR, CD20 and TCR existing in the suspension of ascites-derived exosomes, indicating that the exosomes derived from ovarian cancer patients might be from DC, T cell and B cells.…”

Section: Discussionmentioning

confidence: 99%

Exosomes in the ascites of ovarian cancer patients: origin and effects on anti-tumor immunity

2011

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Abstract. This study was performed to identify the origin of the ascites-derived exosomes from patients with ovarian cancer and to observe the effect of exosomes on anti-tumor immunity. Exosomes were isolated from the ascites of patients with ovarian epithelial cancer by ultracentrifugation plus density gradient centrifugation. The origin of exosomes was identified by immunoelectronmicroscopy (IEM). The growth curve of the tumor cell line SKOV3 cultured with or without exosomes was analyzed. The apoptosis of autogeneic tumor cells (ATCs) and SKOV3 cells affected by exosomes was measured by flow cytometry (FCM) and light phase contrast microscopy. The cytotoxic effect of the peripheral blood mononuclear cells (PBMCs) stimulated by exosomes and/or dendritic cells (DCs) on ovarian cancer cells was measured using a CCK-8 assay. The levels of IFN-Á released by PBMCs stimulated by exosomes and/or DCs were measured by ELISA. The apoptosis of PBMCs and DCs affected by exosomes was measured by FCM and light microscopy. Whether the mature process of DCs was affected by exosomes was studied by FCM. The ratio of CD4 + T cell and CD8 + T cell were measured by FCM. FasL and TRAIL molecules on exosomes were detected by Western blot analysis. The human FasL antagonistic antibody was used to block the apoptosis of DCs and PBMCs induced by exosomes. The receptors of TRAIL DR4 and DR5 on PBMCs and DCs were detected by FCM. In 41 patients examined, we isolated exosomes from the ascites of 35 patients. We detected TCR, CD20, HLA-DR, B7-2, HER2/neu, CA125 and Histone H 2 A on exosomes. We found that exosomes might impair the cytotoxic activity of PBMCs when DCs are present. We found that exosomes had no effect on the growth and apoptosis of SKOV3 cells. However, exosomes may induce apoptosis of precursors, mature DCs and PBMCs. We found that FasL and TRAIL were present in the exosome suspension and addition of an anti-FasL antibody may decrease the percentage of apoptosis of DCs and PBMCs. We conclude that exosomes exist in ascites of 85.4% of patients with ovarian cancer. Moreover, these exosomes may be of multi-origin. Exosomes had no effect on the growth and apoptosis of tumor cells but impaired the cytotoxic activity of PBMCs in the presence of DCs. Exosomes also may induce apoptosis of the precursors of DCs, DCs and PBMCs. FasL and TRAIL on exosomes may partly account for the apoptosis of cells of the immune system.

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Section: Discussionmentioning

confidence: 99%

Exosomes in the ascites of ovarian cancer patients: origin and effects on anti-tumor immunity

2011

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“…Tumor exosomes, which are constitutively released into the extracellular space, have different molecular profiles, biological roles and molecular contents, giving an indication of the cell of origin, as well as their functional role [4][5][6]. This has also been shown in vivo, where membrane vesicles isolated from cancer patients' plasma and neoplastic effusions are characterized by the expression of tumor-specific markers reflecting tumor origin [7][8][9][10].…”

Section: Introductionmentioning

confidence: 92%

Exosomes Secreted from Human Cancer Cell Lines Contain Inhibitors of Apoptosis (IAP)

Valenzuela

Bennit

Gonda

et al. 2015

Cancer Microenvironment

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Exosomes are endosomal-derived nanovesicles released by normal and tumor cells which have been shown to transfer functionally active protein, lipids, mRNAs and miRNAs between cells. Varying in molecular profiles, biological roles, functional roles and protein contents, exosomes have been described as Bmulti-purpose carriers^playing a role in supporting the survival and growth of tumor cells. The IAP Survivin has been found to be present in tumor exosomes. However, the existence of other IAPs in tumor exosomes is still unknown. Survivin, cIAP1, cIAP2 and XIAP mRNA and protein are differently expressed in a panel of tumor cell lines: DLCL2, HeLa, MCF-7, Panc-1, and PC3. Exosomes were isolated from conditioned media collected from the cells from which RNA and protein were extracted. Our results provide evidence that like Survivin, XIAP, cIAP1 and cIAP2 proteins are found in tumor exosomes. The mRNA expression, however, is differentially expressed across the tumor cell lines. The presence of these bioactive molecules in exosomes may not only serve as warning signals, but also play a role in providing protection to the cancer cells against changes that are constantly occurring in the tumor microenvironment.

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“…16 The fact that the hallmark alterations induced by tumour microvesicles on host cells in vitro can also be found in immune cells isolated from cancer patients supports the hypothesis that these negative loops can actually be established in vivo as well. 41,42 As a further proof of the pleiotropic effect of tumour-secreted exosomes, it should be mentioned that tumour exosomes can also interfere directly with T cell effector functions. Indeed, we have recently shown that the • Exosome-transported molecules…”

Section: Tumour Exosomes: a Versatile Tool Of Immune Modulationmentioning

confidence: 99%

Tumour-released exosomes and their implications in cancer immunity

et al. 2007

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Human Tumor-Derived vs Dendritic Cell-Derived Exosomes Have Distinct Biologic Roles and Molecular Profiles

Cited by 115 publications

References 18 publications

Exosomes in the ascites of ovarian cancer patients: origin and effects on anti-tumor immunity

Exosomes in the ascites of ovarian cancer patients: origin and effects on anti-tumor immunity

Exosomes Secreted from Human Cancer Cell Lines Contain Inhibitors of Apoptosis (IAP)

Tumour-released exosomes and their implications in cancer immunity

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