Exosomes

Publication Title: 
Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences

This paper presents a review of recent work on the role that two epigenetic-related systems may play in information processing mechanisms in the brain. The first consists of exosomes that transport epigenetic-related molecules between neurons. The second consists of homeoproteins like Otx2 that carry information from sense organs to primary sensory cortex. There is developing evidence that presynaptic neurons may be able to modulate the fine microanatomical structure in the postsynaptic neuron.

Author(s): 
Edelstein, Lawrence
Smythies, John
Publication Title: 
International Journal of Cancer. Journal International Du Cancer

Myeloid-derived suppressor cells (MDSCs) promote tumor progression. The mechanisms of MDSC development during tumor growth remain unknown. Tumor exosomes (T-exosomes) have been implicated to play a role in immune regulation, however the role of exosomes in the induction of MDSCs is unclear. Our previous work demonstrated that exosomes isolated from tumor cells are taken up by bone marrow myeloid cells. Here, we extend those findings showing that exosomes isolated from T-exosomes switch the differentiation pathway of these myeloid cells to the MDSC pathway (CD11b(+)Gr-1(+)).

Author(s): 
Xiang, Xiaoyu
Poliakov, Anton
Liu, Cunren
Liu, Yuelong
Deng, Zhong-Bin
Wang, Jianhua
Cheng, Ziqiang
Shah, Spandan V.
Wang, Gui-Jun
Zhang, Liming
Grizzle, William E.
Mobley, Jim
Zhang, Huang-Ge
Publication Title: 
The American Journal of Pathology

Ubiquitinated endosomal proteins that are deposited into the lumens of multivesicular bodies are either sorted for lysosomal-mediated degradation or secreted as exosomes into the extracellular milieu. The mechanisms that underlie the sorting of cellular cargo proteins are currently unknown. In this study, we show that the COP9 signalosome (CSN)-associated protein CSN5 quantitatively regulated proteins that were sorted into exosomes.

Author(s): 
Liu, Yuelong
Shah, Spandan V.
Xiang, Xiaoyu
Wang, Jianhua
Deng, Zhong-Bin
Liu, Cunren
Zhang, Liming
Wu, Jianming
Edmonds, Tara
Jambor, Christina
Kappes, John C.
Zhang, Huang-Ge
Publication Title: 
Journal of Proteome Research

Exosomes represent a discrete population of vesicles that are secreted from various cell types to the extracellular media. Their protein and lipid composition are a consequence of sorting events at the level of the multivesicular body, a central organelle which integrates endocytic and secretory pathways. Characterization of exosomes from different biological samples has shown the presence of common as well as cell-type specific proteins. Remarkably, the protein content of the exosomes is modified upon pathological or stress conditions.

Author(s): 
Conde-Vancells, Javier
Rodríguez-Suárez, Eva
Embade, Nieves
Gil, David
Matthiesen, Rune
Valle, Mikel
Elortza, Felix
Lu, Shelly C.
Mato, José M.
Falcon-Perez, Juan M.
Publication Title: 
Diabetes

OBJECTIVE: We sought to determine whether exosome-like vesicles (ELVs) released from adipose tissue play a role in activation of macrophages and subsequent development of insulin resistance in a mouse model. RESEARCH DESIGN AND METHODS: ELVs released from adipose tissue were purified by sucrose gradient centrifugation and labeled with green fluorescent dye and then intravenously injected into B6 ob/ob mice (obese model) or B6 mice fed a high-fat diet.

Author(s): 
Deng, Zhong-Bin
Poliakov, Anton
Hardy, Robert W.
Clements, Ronald
Liu, Cunren
Liu, Yuelong
Wang, Jianhua
Xiang, Xiaoyu
Zhang, Shuangqin
Zhuang, Xiaoying
Shah, Spandan V.
Sun, Dongmei
Michalek, Sue
Grizzle, William E.
Garvey, Timothy
Mobley, Jim
Zhang, Huang-Ge
Publication Title: 
Expert Opinion on Drug Metabolism & Toxicology

IMPORTANCE OF THE FIELD: Liver is the major body reservoir for enzymes involved in the metabolism of endogenous and xenobiotic compounds. Recently, it has been shown that hepatocytes release exosome-like vesicles to the extracellular medium, and the proteomic characterization of these hepatocyte-secreted exosomes has revealed the presence of several of these enzymes on them.

Author(s): 
Conde-Vancells, Javier
Gonzalez, Esperanza
Lu, Shelly C.
Mato, José M.
Falcon-Perez, Juan M.
Publication Title: 
The American Journal of Pathology

In this study we observed that mice pretreated with tumor exosomes had a significant acceleration of tumor metastasis in the lung. Tumor metastasis correlated significantly with an increase in recruitment of more Myeloid-derived suppressor cells (MDSCs) in the lung of C57BL/6j (B6) mice pretreated with tumor exosomes. These effects were blunted when MyD88 knockout (KO) mice were pretreated with tumor exosomes.

Author(s): 
Liu, Yuelong
Xiang, Xiaoyu
Zhuang, Xiaoying
Zhang, Shuangyin
Liu, Cunren
Cheng, Ziqiang
Michalek, Sue
Grizzle, William
Zhang, Huang-Ge
Publication Title: 
Proteomics. Clinical Applications

PURPOSE: There is a compelling clinical imperative to identify discerning molecular biomarkers of hepatic disease in order to inform the diagnosis, prognosis and treatment. EXPERIMENTAL DESIGN: We have investigated the proteome of urinary vesicles present in urine samples obtained from experimental models for the study of liver injury, as an approach for identifying potential biomarkers for hepatic disease.

Author(s): 
Conde-Vancells, Javier
Rodríguez-Suárez, Eva
Gonzalez, Esperanza
Berisa, Agustin
Gil, David
Embade, Nieves
Valle, Mikel
Luka, Zigmund
Elortza, Felix
Wagner, Conrad
Lu, Shelly C.
Mato, José M.
Falcon-Perez, M.
Publication Title: 
Molecular Therapy: The Journal of the American Society of Gene Therapy

Monocyte-derived myeloid cells play vital roles in inflammation-related autoimmune/inflammatory diseases and cancers. Here, we report that exosomes can deliver anti-inflammatory agents, such as curcumin, to activated myeloid cells in vivo. This technology provides a means for anti-inflammatory drugs, such as curcumin, to target the inflammatory cells as well as to overcome unwanted off-target effects that limit their utility. Using exosomes as a delivery vehicle, we provide evidence that curcumin delivered by exosomes is more stable and more highly concentrated in the blood.

Author(s): 
Sun, Dongmei
Zhuang, Xiaoying
Xiang, Xiaoyu
Liu, Yuelong
Zhang, Shuangyin
Liu, Cunren
Barnes, Stephen
Grizzle, William
Miller, Donald
Zhang, Huang-Ge
Publication Title: 
The American Journal of Pathology

Exosomes released from tumor cells having been shown to induce interleukin-6 release from myeloid-derived suppressor cells in a Toll-like receptor 2/Stat3-dependent manner. In this study, we show that exosomes released from tumor cells re-isolated from syngeneic mice are capable of inducing interleukin-6 in a Toll-like receptor 2-independent manner, whereas the data generated from exosomes of tumor cells having undergone numerous in vitro passages induce interleukin-6 in a Toll-like receptor 2-dependent manner.

Author(s): 
Xiang, Xiaoyu
Liu, Yuelong
Zhuang, Xiaoyin
Zhang, Shuangqin
Michalek, Sue
Taylor, Douglas D.
Grizzle, William
Zhang, Huang-Ge

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