Decoding the Biology of Exosomes in Metastasis

doi:10.1016/j.trecan.2019.11.007

Trends in Cancer

Volume 6, Issue 1, January 2020, Pages 20-30

https://doi.org/10.1016/j.trecan.2019.11.007 Get rights and content

Highlights

Metastasis organotropism is not entirely explained by the anatomy of the blood and lymphatic circulatory networks. Other factors influence metastatic cells’ ability to seed and prosper in a host organ, including its microenvironment and specific cues originating from the tumor of origin.
Exosomes have been proposed to be both short- and long-distance mediators of intercellular communication through the modulation of recipient cells on ligand–receptor interaction and/or cargo release.
In addition to cancer exosomes, exosomes derived from other cells of the tumor microenvironment have been described as key players in the various steps of the metastatic cascade.
Exosomes derived from the primary tumor influence circulating tumor cells to enhance their tumor self-seeding ability.

Metastasis is the leading cause of cancer mortality. Cancer cells must adapt to colonize and thrive at the metastatic site. The modulation of the receptive organ microenvironment is a key event in the adaptation process and is partially accomplished at a distance by the primary tumor. Exosomes, a subclass of extracellular vesicles (EVs), are distal mediators of communication that carry genetic and molecular information to neighboring and distant cells. Cancer exosomes have been involved in restructuring metastatic sites to support cancer cell colonization. In this article, we discuss the role of exosomes in the metastatic process.

Section snippets

Cancer Exosomes

A large body of evidence has shown that virtually all organisms, despite their complexity and diversity, secrete EVs. This secretion appears to be a conserved mechanism across all three domains of life: Archaea, Bacteria, and Eukarya [1]. EVs have been found in all human body fluids tested to date, including urine, saliva, cerebrospinal fluid, milk, blood, and ascites [2]. Since EVs are easily accessible and the content reflects the biological context of their cell of origin, they are an

Tumor Growth and Local Invasion

If a tumor is considered a foreign entity growing in a body, this entity can be understood as trying to influence the host tissues to survive and prosper; the metastatic cascade is a clear reflection of this. To colonize other organs, cancer cells adopt various strategies to survive and grow at a distance on leaving the primary tumor [14]. The invasion of cancer cells is one of the early steps in the metastatic cascade. Cancer exosomes contribute directly to this event by remodeling the

Concluding Remarks

The current state of the art focuses predominantly on the identification of exosomal functions throughout the various stages of tumor development. Based on the current observations, little doubt remains on the important role played by these EVs in cancer. Nevertheless, the function of exosomes from the metastasis at the metastatic site remains largely unexplored (see Outstanding Questions). Importantly, most of the evidence gathered to date was obtained from in vitro experiments or in vivo

Acknowledgments

The laboratory is supported by the European Regional Development Fund (ERDF) through COMPETE 2020 – Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by FCT – Fundação para a Ciência e a Tecnologia (FCT)/Ministério da Ciência, Tecnologia e Inovação in the framework of the project ‘Institute for Research and Innovation in Health Sciences’ POCI-01-0145-FEDER-032189; by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership

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⁶: These authors contributed equally to this work.

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Trends in Cancer

OpinionDecoding the Biology of Exosomes in Metastasis

Highlights

Section snippets

Cancer Exosomes

Tumor Growth and Local Invasion

Concluding Remarks

Acknowledgments

Semin. Cell Dev. Biol.

Cancer Cell

Cancer Cell

Nature

Blood

Trends Cell Biol.

Cell

Biochem. Biophys. Res. Commun.

Dev. Cell

Int. J. Biochem. Cell Biol.

Curr. Biol.

Cancer Lett.

Thromb. Res.

Gene

Transl. Oncol.

Extracellular membrane vesicles in the three domains of life and beyond

FEMS Microbiol. Rev.

The biology and function of exosomes in cancer

J. Clin. Invest.

Glypican-1 identifies cancer exosomes and detects early pancreatic cancer

Nature

Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles

Annu. Rev. Cell Dev. Biol.

Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes

Proc. Natl Acad. Sci. U. S. A.

The fate of the transferrin receptor during maturation of sheep reticulocytes in vitro

Can. J. Biochem. Cell Biol.

Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells

Nat. Cell Biol.

The biology of cancer exosomes: insights and new perspectives

Cancer Res.

Exosomes

Annu. Rev. Biochem.

Shedding light on the cell biology of extracellular vesicles

Nat. Rev. Mol. Cell Biol.

Cell–cell communication in the tumor microenvironment, carcinogenesis, and anticancer treatment

Cell. Physiol. Biochem.

Exosomes at a glance – common nominators for cancer hallmarks and novel diagnosis tools

Crit. Rev. Biochem. Mol. Biol.

A perspective on cancer cell metastasis

Science

Host matrix modulation by tumor exosomes promotes motility and invasiveness

Neoplasia

Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability

Carcinogenesis

Cancer exosomes trigger fibroblast to myofibroblast differentiation

Cancer Res.

Differentiation of tumour-promoting stromal myofibroblasts by cancer exosomes

Oncogene

Extracellular vesicles direct migration by synthesizing and releasing chemotactic signals

J. Cell Biol.

Directional cell movement through tissues is controlled by exosome secretion

Nat. Commun.

Angiogenesis in cancer

Vasc. Health Risk Manag.

Cell surface tetraspanin Tspan8 contributes to molecular pathways of exosome-induced endothelial cell activation

Cancer Res.

WNT5A induces release of exosomes containing pro-angiogenic and immunosuppressive factors from malignant melanoma cells

Mol. Cancer

Opinion
Decoding the Biology of Exosomes in Metastasis