Microvesicles provide a mechanism for intercellular communication by embryonic stem cells during embryo implantation

Desrochers, Laura M.; Bordeleau, François; Reinhart‐King, Cynthia A.; Cerione, Richard A.; Antonyak, Marc A.

doi:10.1038/ncomms11958

Cited by 192 publications

(188 citation statements)

References 64 publications

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“…Exosomes are mediators of cell-to-cell communication that carry unique molecular signatures [35–37]. hESCs can produce a significant amount of exosomes that can exert different physiological effects both in vitro and in vivo, and could therefore be used as a new tool to reprogram malignant cancer cells via transfer of bioactive proteins, and nucleic acids into target cells [23, 38]. Herein, we report that hESCs-Exo transfer a full network of embryonic pluripotency transcription factors, not just a single pluripotency factor, into cancer cells thus leading to the reprograming of cancer cells to a more benign state by reducing cancer cells tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Reprogramming Malignant Cancer Cells toward a Benign Phenotype following Exposure to Human Embryonic Stem Cell Microenvironment

et al. 2017

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The embryonic microenvironment is well known to be non-permissive for tumor development because early developmental signals naturally suppress the expression of proto-oncogenes. In an analogous manner, mimicking an early embryonic environment during embryonic stem cell culture has been shown to suppress oncogenic phenotypes of cancer cells. Exosomes derived from human embryonic stem cells harbor substances that mirror the content of the cells of origin and have been reported to reprogram hematopoietic stem/progenitor cells via horizontal transfer of mRNA and proteins. However, the possibility that these embryonic stem cells-derived exosomes might be the main effectors of the anti-tumor effect mediated by the embryonic stem cells has not been explored yet. The present study aims to investigate whether exosomes derived from human embryonic stem cells can reprogram malignant cancer cells to a benign stage and reduce their tumorigenicity. We show that the embryonic stem cell-conditioned medium contains factors that inhibit cancer cell growth and tumorigenicity in vitro and in vivo. Moreover, we demonstrate that exosomes derived from human embryonic stem cells display anti-proliferation and pro-apoptotic effects, and decrease tumor size in a xenograft model. These exosomes are also able to transfer their cargo into target cancer cells, inducing a dose-dependent increase in SOX2, OCT4 and Nanog proteins, leading to a dose-dependent decrease of cancer cell growth and tumorigenicity. This study shows for the first time that human embryonic stem cell-derived exosomes play an important role in the tumor suppressive activity displayed by human embryonic stem cells.

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Section: Discussionmentioning

confidence: 99%

Reprogramming Malignant Cancer Cells toward a Benign Phenotype following Exposure to Human Embryonic Stem Cell Microenvironment

et al. 2017

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“…After fusion, EV shedding from the fertilized egg inhibits polyspermy by rapid removal of the sperm receptor from the plasma membrane [103]. In the early embryo, EVs released by stem cells in the inner cell mass contain laminin and fibronectin which bind to integrins on the trophoblasts, leading to activation of JNK and focal adhesion kinase (FAK) pathways promoting migration and implantation [104]. …”

Section: Physiological Roles Of Evsmentioning

confidence: 99%

Extracellular Vesicles: Unique Intercellular Delivery Vehicles

Maas

Breakefield

Weaver

2017

Trends in Cell Biology

1,125

969

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Extracellular vesicles (EVs) are a heterogeneous collection of membrane-bound carriers with complex cargos, including proteins, lipids and nucleic acids. While release of EVs was previously thought to be only a mechanism to discard nonfunctional cellular components, increasing evidence implicates EVs as key players in intercellular and even interorganismal communication. EVs confer stability and can direct their cargoes to specific cell types. EV cargoes also appear to act in a combinatorial manner to communicate directives to other cells. This review will focus on recent findings and knowledge gaps in the area of EV biogenesis, release, and uptake. In addition, we highlight examples whereby EV cargoes control basic cellular functions, including motility and polarization, immune responses, and development, as well as contribute to diseases, such as cancer and neurodegeneration.

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“…[6][7][8][9][10][11] Additional extracellular vesicles (EVs), known as microvesicles (MVs), are shed from the surface of cells and also have been implicated in numerous biologic phenotypes, including embryonic stem cell communication, oncogenic transformation, and inflammation. [12][13][14][15] A major function of exosomes appears to be promotion of cell motility. 6,10,[16][17][18] Thus, exosomes have been shown to promote cell protrusion formation, 16 adhesion, 6,19 and cell polarity.…”

Section: Introductionmentioning

confidence: 99%

Exosome secretion promotes chemotaxis of cancer cells

Sung

Weaver

2017

Cell Adhesion & Migration

102

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Migration of cells toward chemical cues, or chemotaxis, is important for many biologic processes such as immune defense, wound healing and cancer metastasis. Although chemotaxis is thought to occur in cancer cells, it is less well characterized than chemotaxis of professional immune cells such as neutrophils. Here, we show that cancer cell chemotaxis relies on secretion of exosome-type extracellular vesicles. Migration of fibrosarcoma cells toward a gradient of exosome-depleted serum was diminished by knockdown of the exosome secretion regulator Rab27a. Rescue experiments in which chemotaxis chambers were coated with purified extracellular vesicles demonstrate that exosomes but not microvesicles affect both speed and directionality of migrating cells. Chamber coating with purified fibronectin and fibronectin-depleted exosomes demonstrates that the exosome cargo fibronectin promotes cell speed but cannot account for the role of exosomes in promoting directionality of fibrosarcoma cell movement during chemotaxis. These experiments indicate that exosomes contain multiple motility-promoting cargoes that contribute to different aspects of cell motility.

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Microvesicles provide a mechanism for intercellular communication by embryonic stem cells during embryo implantation

Cited by 192 publications

References 64 publications

Reprogramming Malignant Cancer Cells toward a Benign Phenotype following Exposure to Human Embryonic Stem Cell Microenvironment

Reprogramming Malignant Cancer Cells toward a Benign Phenotype following Exposure to Human Embryonic Stem Cell Microenvironment

Extracellular Vesicles: Unique Intercellular Delivery Vehicles

Exosome secretion promotes chemotaxis of cancer cells

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