Cancer exosomes trigger fibroblast to myofibroblast differentiation.
AuthorsWebber J, Steadman R, Mason MD, Tabi Z, Clayton A,
JournalCancer Res
PubMed ID21098712
There is a growing interest in the cell-cell communication roles in cancer mediated by secreted vesicles termed exosomes. In this study, we examined whether exosomes produced by cancer cells could transmit information to normal stromal fibroblasts and trigger a cellular response. We found that some cancer-derived exosomes could trigger elevated ... More
Targeting tumor antigens to secreted membrane vesicles in vivo induces efficient antitumor immune responses.
AuthorsZeelenberg IS, Ostrowski M, Krumeich S, Bobrie A, Jancic C, Boissonnas A, Delcayre A, Le Pecq JB, Combadière B, Amigorena S, Théry C,
JournalCancer Res
PubMed ID18281500
'Expression of non-self antigens by tumors can induce activation of T cells in vivo, although this activation can lead to either immunity or tolerance. CD8+ T-cell activation can be direct (if the tumor expresses MHC class I molecules) or indirect (after the capture and cross-presentation of tumor antigens by dendritic ... More
Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes.
AuthorsWahlgren J, De L Karlson T, Brisslert M, Vaziri Sani F, Telemo E, Sunnerhagen P, Valadi H,
JournalNucleic Acids Res
PubMed ID22618874
'Despite the promise of RNA interference (RNAi) and its potential, e.g. for use in cancer therapy, several technical obstacles must first be overcome. The major hurdle of RNAi-based therapeutics is to deliver nucleic acids across the cell''s plasma membrane. This study demonstrates that exosome vesicles derived from humans can deliver ... More
Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis.
AuthorsFitzner D, Schnaars M, van Rossum D, Krishnamoorthy G, Dibaj P, Bakhti M, Regen T, Hanisch UK, Simons M,
JournalJ Cell Sci
PubMed ID21242314
'The transfer of antigens from oligodendrocytes to immune cells has been implicated in the pathogenesis of autoimmune diseases. Here, we show that oligodendrocytes secrete small membrane vesicles called exosomes, which are specifically and efficiently taken up by microglia both in vitro and in vivo. Internalisation of exosomes occurs by a ... More
Exosomal evasion of humoral immunotherapy in aggressive B-cell lymphoma modulated by ATP-binding cassette transporter A3.
'Targeting the surface of malignant cells has evolved into a cornerstone in cancer therapy, paradigmatically introduced by the success of humoral immunotherapy against CD20 in malignant lymphoma. However, tumor cell susceptibility to immunochemotherapy varies, with mostly a fatal outcome in cases of resistant disease. Here, we show that lymphoma exosomes ... More
Proteomic and immunologic analyses of brain tumor exosomes.
AuthorsGraner MW, Alzate O, Dechkovskaia AM, Keene JD, Sampson JH, Mitchell DA, Bigner DD,
JournalFASEB J
PubMed ID19109410
'Brain tumors are horrific diseases with almost universally fatal outcomes; new therapeutics are desperately needed and will come from improved understandings of glioma biology. Exosomes are endosomally derived 30-100 nm membranous vesicles released from many cell types into the extracellular milieu; surprisingly, exosomes are virtually unstudied in neuro-oncology. These microvesicles ... More
Anticancer drugs cause release of exosomes with heat shock proteins from human hepatocellular carcinoma cells that elicit effective natural killer cell antitumor responses in vitro.
AuthorsLv LH, Wan YL, Lin Y, Zhang W, Yang M, Li GL, Lin HM, Shang CZ, Chen YJ, Min J,
JournalJ Biol Chem
PubMed ID22396543
Failure of immune surveillance related to inadequate host antitumor immune responses has been suggested as a possible cause of the high incidence of recurrence and poor overall survival outcome of hepatocellular carcinoma. The stress-induced heat shock proteins (HSPs) are known to act as endogenous ... More
Immune surveillance properties of human NK cell-derived exosomes.
AuthorsLugini L, Cecchetti S, Huber V, Luciani F, Macchia G, Spadaro F, Paris L, Abalsamo L, Colone M, Molinari A, Podo F, Rivoltini L, Ramoni C, Fais S,
JournalJ Immunol
PubMed ID22904309
Exosomes are nanovesicles released by normal and tumor cells, which are detectable in cell culture supernatant and human biological fluids, such as plasma. Functions of exosomes released by ... More
Exosome release of ADAM15 and the functional implications of human macrophage-derived ADAM15 exosomes.
AuthorsLee HD, Koo BH, Kim YH, Jeon OH, Kim DS,
JournalFASEB J
PubMed ID22505472
A disintegrin and metalloproteinase 15 (ADAM15), the only ADAM protein containing an Arg-Gly-Asp (RGD) motif in its disintegrin-like domain, is a widely expressed membrane protein that is involved in tumor progression and suppression. However, the underlying mechanism of ADAM15-mediated tumor suppression is not clearly understood. This study demonstrates that ADAM15 ... More
Activated T cell exosomes promote tumor invasion via Fas signaling pathway.
AuthorsCai Z, Yang F, Yu L, Yu Z, Jiang L, Wang Q, Yang Y, Wang L, Cao X, Wang J,
JournalJ Immunol
PubMed ID22573809
Activated T cells release bioactive Fas ligand (FasL) in exosomes, which subsequently induce self-apoptosis of T cells. However, their potential effects on cell apoptosis in tumors are still unknown. In this study, we purified exosomes expressing FasL from activated CD8(+) T cell from OT-I mice and found that activated T ... More
Antigen localization controls T cell-mediated tumor immunity.
AuthorsZeelenberg IS, van Maren WW, Boissonnas A, Van Hout-Kuijer MA, Den Brok MH, Wagenaars JA, van der Schaaf A, Jansen EJ, Amigorena S, Théry C, Figdor CG, Adema GJ,
JournalJ Immunol
PubMed ID21705625
Effective antitumor immunotherapy requires the identification of suitable target Ags. Interestingly, many of the tumor Ags used in clinical trials are present in preparations of secreted tumor vesicles (exosomes). In this study, we compared T cell responses elicited by murine MCA101 fibrosarcoma tumors expressing a model Ag at different localizations ... More
Calcium regulates key components of vascular smooth muscle cell-derived matrix vesicles to enhance mineralization.
AuthorsKapustin AN, Davies JD, Reynolds JL, McNair R, Jones GT, Sidibe A, Schurgers LJ, Skepper JN, Proudfoot D, Mayr M, Shanahan CM,
JournalCirc Res
PubMed ID21566214
Matrix vesicles (MVs) are specialized structures that initiate mineral nucleation during physiological skeletogenesis. Similar vesicular structures are deposited at sites of pathological vascular calcification, and studies in vitro have shown that elevated levels of extracellular calcium (Ca) can induce mineralization of vascular smooth muscle cell (VSMC)-derived MVs. To determine the ... More
Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins.
AuthorsSubra C, Grand D, Laulagnier K, Stella A, Lambeau G, Paillasse M, De Medina P, Monsarrat B, Perret B, Silvente-Poirot S, Poirot M, Record M,
JournalJ Lipid Res
PubMed ID20424270
Exosomes are bioactive vesicles released from multivesicular bodies (MVB) by intact cells and participate in intercellular signaling. We investigated the presence of lipid-related proteins and bioactive lipids in RBL-2H3 exosomes. Besides a phospholipid scramblase and a fatty acid binding protein, the exosomes contained the whole set of phospholipases (A2, C, ... More
Tumor-derived microvesicles promote regulatory T cell expansion and induce apoptosis in tumor-reactive activated CD8+ T lymphocytes.
AuthorsWieckowski EU, Visus C, Szajnik M, Szczepanski MJ, Storkus WJ, Whiteside TL,
JournalJ Immunol
PubMed ID19692638
Sera of patients with cancer contain membraneous microvesicles (MV) able to induce apoptosis of activated T cells by activating the Fas/Fas ligand pathway. However, the cellular origin of MV found in cancer patients' sera varies as do their molecular and cellular profiles. To distinguish tumor-derived MV in cancer patients' sera, ... More
More efficient induction of HLA-A*0201-restricted and carcinoembryonic antigen (CEA)-specific CTL response by immunization with exosomes prepared from heat-stressed CEA-positive tumor cells.
AuthorsDai S, Wan T, Wang B, Zhou X, Xiu F, Chen T, Wu Y, Cao X,
JournalClin Cancer Res
PubMed ID16243831
Tumor-derived exosomes are proposed as a new type of cancer vaccine. Heat shock proteins are potent Th1 adjuvant, and heat stress can induce heat shock protein and MHC-I expression in tumor cells, leading to the increased immunogenicity of tumor cells. To improve the immunogenicity of exosomes as cancer vaccine, we ... More
Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells.
AuthorsGastpar R, Gehrmann M, Bausero MA, Asea A, Gross C, Schroeder JA, Multhoff G,
JournalCancer Res
PubMed ID15958569
Detergent-soluble membrane vesicles are actively released by human pancreas (Colo-/Colo+) and colon (CX-/CX+) carcinoma sublines, differing in their capacity to present heat shock protein 70 (Hsp70)/Bag-4 on their plasma membranes. Floating properties, acetylcholine esterase activity, and protein composition characterized them as exosomes. An enrichment of Rab-4 documented their intracellular transport ... More
Alternative mechanism by which IFN-gamma enhances tumor recognition: active release of heat shock protein 72.
AuthorsBausero MA, Gastpar R, Multhoff G, Asea A,
JournalJ Immunol
PubMed ID16116176
IFN-gamma exhibits differential effects depending on the target and can induce cellular activation and enhance survival or mediate cell death via activation of apoptotic pathways. In this study, we demonstrate an alternative mechanism by which IFN-gamma enhances tumor recognition, mediated by the active release of Hsp72. We demonstrate that stimulation ... More
Lipid raft-associated protein sorting in exosomes.
Authorsde Gassart A, Geminard C, Fevrier B, Raposo G, Vidal M,
JournalBlood
PubMed ID12881314
Exosomes are small membrane vesicles secreted by cells upon fusion of multivesicular endosomes with the cell surface. The mechanisms underlying the specific sorting of proteins in exosomal membranes are far from being unraveled. We demonstrate here, using different cells, that some molecules are released in the extracellular medium via their ... More
ATP-binding cassette transporter A7 enhances phagocytosis of apoptotic cells and associated ERK signaling in macrophages.
AuthorsJehle AW, Gardai SJ, Li S, Linsel-Nitschke P, Morimoto K, Janssen WJ, Vandivier RW, Wang N, Greenberg S, Dale BM, Qin C, Henson PM, Tall AR
JournalJ Cell Biol
PubMed ID16908670
The mammalian ATP-binding cassette transporters A1 and A7 (ABCA1 and -A7) show sequence similarity to CED-7, a Caenorhabditis elegans gene that mediates the clearance of apoptotic cells. Using RNA interference or gene targeting, we show that knock down of macrophage ABCA7 but not -A1 results in defective engulfment of apoptotic ... More