Unraveling the physiological functions of exosome secretion by tumors

Bobrie, Angélique; Théry, Clotilde

doi:10.4161/onci.22565

Cited by 37 publications

(30 citation statements)

References 10 publications

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“…Heparanase, an enzyme overexpressed in in many tumor cell lines, was recently reported to regulate exosome secretion [29]. The Rap GTPase proteins, especially Rab27a and Rab27b, controlling the secretory pathways are strongly implicated in exosome release [30, 31]. Knock down of Rab proteins has been shown to decrease exosome secretion by tumor cells [31, 32].…”

Section: Exosome Biogenesis In Cancermentioning

confidence: 99%

“…The Rap GTPase proteins, especially Rab27a and Rab27b, controlling the secretory pathways are strongly implicated in exosome release [30, 31]. Knock down of Rab proteins has been shown to decrease exosome secretion by tumor cells [31, 32]. To date, the mechanisms tumor cells employ to regulate exosome secretion remain unknown, although emerging insights suggest that several distinct mechanisms may be involved and may depend on the cancer type and its aggressiveness.…”

Section: Exosome Biogenesis In Cancermentioning

confidence: 99%

“…Also, exosome secretion could potentially be modulated by interfering with functions of the endo-lysosomal compartments in cells via proton pump inhibitors [70]. Uptake of exosomes could also be targeted and potentially attenuated by blocking surface adhesion molecules, for example, phosphatidylserine, ICAM1, cell surface heparin sulfate proteoglycans or of other receptors participating in exosome internalization [31, 105]. Targeting of intracellular signaling pathways activated by exosomes or oncogenes delivered to recipient cells by the use of inhibitory RNAs (RNAi) is being also explored [32].…”

Section: 0 Tumor-derived Exosomes and Cancer Immunotherapymentioning

confidence: 99%

See 2 more Smart Citations

Tumor-Derived Exosomes and Their Role in Cancer Progression

Whiteside

2016

Advances in Clinical Chemistry

583

492

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Tumor cells actively produce, release and utilize exosomes to promote tumor growth. Mechanisms through which tumor-derived exosomes subserve the tumor are under intense investigation. These exosomes are information carriers, conveying molecular and genetic messages from tumor cells to normal or other abnormal cells residing at close or distant sites. Tumor-derived exosomes are found in all body fluids. Upon the contact with target cells, they alter phenotypic and functional attributes of recipients, reprogramming them into active contributors to angiogenesis, thrombosis, metastasis and immunosuppression. Exosomes produced by tumors carry cargos that in part mimic contents of parent cells and are of potential interest as non-invasive biomarkers of cancer. Their role in inhibiting the host antitumor responses and in mediating drug resistance is important for cancer therapy. Tumor-derived exosomes may interfere with cancer immunotherapy, but they also could serve as adjuvants and antigenic components of antitumor vaccines. Their biological roles in cancer development or progression as well as cancer therapy suggest that tumor-derived exosomes are critical components of oncogenic transformation.

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Section: Exosome Biogenesis In Cancermentioning

confidence: 99%

Section: Exosome Biogenesis In Cancermentioning

confidence: 99%

Section: 0 Tumor-derived Exosomes and Cancer Immunotherapymentioning

confidence: 99%

See 1 more Smart Citation

Tumor-Derived Exosomes and Their Role in Cancer Progression

Whiteside

2016

Advances in Clinical Chemistry

583

492

View full text Add to dashboard Cite

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“…Specifically, exosomes have been reported to transport proteins and coding and non-coding RNA between cells. 41,42 Results of our pathway enrichment analysis suggest that these exosomes alter the metabolic profile of immune cells that enter the tumor microenvironment by delivering a collection of metabolic enzymes and alter antigen presentation. Moreover, the size of exosomes also suggests that their diffusivity within tissues may help create spatial gradients.…”

Section: Resultsmentioning

confidence: 98%

Eavesdropping on altered cell-to-cell signaling in cancer by secretome profiling

Klinke

2015

Molecular & Cellular Oncology

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In the past decade, cumulative clinical experiences with molecular targeted therapies and immunotherapies for cancer have promoted a shift in our conceptual understanding of cancer. This view shifted from viewing solid tumors as a homogeneous mass of malignant cells to viewing tumors as heterogeneous structures that are dynamically shaped by intercellular interactions among the variety of stromal, immune, and malignant cells present within the tumor microenvironment. As in any dynamic system, identifying how cells communicate to maintain homeostasis and how this communication is altered during oncogenesis are key hurdles for developing therapies to restore normal tissue homeostasis. Here, I discuss tissues as dynamic systems, using the mammary gland as an example, and the evolutionary concepts applied to oncogenesis. Drawing from these concepts, I present 2 competing hypotheses for how intercellular communication might be altered during oncogenesis. As an initial test of these competing hypotheses, a recent secretome comparison between normal human mammary and HER2C breast cancer cell lines suggested that the particular proteins secreted by the malignant cells reflect a convergent evolutionary path associated with oncogenesis in a specific anatomical niche, despite arising in different individuals. Overall, this study illustrates the emerging power of secretome proteomics to probe, in an unbiased way, how intercellular communication changes during oncogenesis.

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“…In experiments involving HIV-1-infected lymphocytes, HIV-1 infection has been shown to affect exosome release and the exosome-associated proteins Tsg101 and Alix (Li et al , 2012). Of the metabolic changes associated with Vpr, ROS accumulation leading to HIF-1α activation, changes in ceramide synthesis, and increases in Ca 2+ due to mitochondrial instability are all known triggers of exosomal release (Bobrie and Thery, 2013; King et al , 2012; Simons and Raposo, 2009). In many in vitro studies, these mechanisms are exploited to induce exosomal release.…”

Section: Possible Roles For Vpr In Exosome Biologymentioning

confidence: 99%

Defining the roles for Vpr in HIV-1-associated neuropathogenesis

et al. 2016

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It is increasingly evident that the human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) has a unique role in neuropathogenesis. Its ability to induce G2/M arrest coupled with its capacity to increase viral gene transcription gives it a unique role in sustaining viral replication and aiding in the establishment and maintenance of a systemic infection. The requirement of Vpr for HIV-1 infection and replication in cells of monocytic origin (a key lineage of cells involved in HIV-1 neuroinvasion) suggests an important role in establishing and sustaining infection in the central nervous system (CNS). Contributions of Vpr to neuropathogenesis can be expanded further through (i) naturally occurring HIV-1 sequence variation that results in functionally divergent Vpr variants; (ii) the dual activities of Vpr as a intracellular protein delivered and expressed during HIV-1 infection and as an extracellular protein that can act on neighboring, uninfected cells; (iii) cell type-dependent consequences of Vpr expression and exposure, including cell cycle arrest, metabolic dysregulation, and cytotoxicity; and (iv) the effects of Vpr on exosome-based intercellular communication in the CNS. Revealing the effects of this pleiotropic viral protein is an essential part of a greater understanding of HIV-1-associated pathogenesis and potential approaches to treating and preventing disease caused by HIV-1 infection.

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Unraveling the physiological functions of exosome secretion by tumors

Cited by 37 publications

References 10 publications

Tumor-Derived Exosomes and Their Role in Cancer Progression

Tumor-Derived Exosomes and Their Role in Cancer Progression

Eavesdropping on altered cell-to-cell signaling in cancer by secretome profiling

Defining the roles for Vpr in HIV-1-associated neuropathogenesis

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