The role of exosomes on colorectal cancer: A review
Lidia Ruiz-López,* Isabel Blancas,*
José M Garrido,*
Nuria Mut-Salud,* Marta Moya-Jódar,*
and Fernando Rodríguez-Serrano*
*Institute of Biopathology and Regenerative Medicine (IBIMER),
Molecular Biochemistry and Parasitology Research Group, Department of Parasitology,
Institute of Biotechnology, Faculty of Sciences, **Department of Human Anatomy and Embryology, University of Granada,
Biosanitary Research Institute
of Granada (ibs.GRANADA),
Department of Oncology, San Cecilio University Hospital, and
Department of Cardiovascular Surgery, Virgen de las Nieves
University Hospital, Granada, Spain
biomarkers, colorectal cancer, exosomes,
intercellular communication, oncogenic
Accepted for publication 10 November 2017.
Dr Fernando Rodríguez-Serrano, Institute of
Biopathology and Regenerative Medicine.
Biomedical Research Centre. Av. del
Conocimiento, s/n. 18100 Armilla, Granada,
Declaration of conflicts of interest: This work
was supported by grants from the Ministry of
Economy and Competitiveness (Project
CTQ2014-56611-R), the Regional Government
of Andalusia (Project P11-CTS-7651), and
Ramón Areces Foundation (Madrid, Spain).
None of the authors has any potential conﬂicts
of interest related to this article to declare.
Exosomes are extracellular microvesicles released from cells, which are involved in many
biological and pathological processes, mainly because of their role in intercellular
communication. Exosomes derived from colorectal cancer (CRC) cells are related to
oncogenesis, tumor cell survival, chemo-resistance, and metastasis. The role of the
exosomes in these processes involves the transfer of proteins, RNAs, or mutant versions
of proto-oncogenes to the target cells. In recent years, great efforts have been made to
identify useful biomarkers in CRC exosomes for diagnosis, prediction of prognosis, and
treatment response. This review focuses on recent studies on CRC exosomes, considering
isolation, cargo, biomarkers, and the effects of exosomes on the development and
progression of CRC, including resistance to antitumor therapy.
In 2012, colorectal cancer (CRC) was the most common type of can-
cer of the digestive system in the world. In terms of gender, CRC was
the third most common tumor in men and the second in women
worldwide. Countries with a high human development index are
the most affected by CRC. Considering demographic factors, the
global burden of CRC is expected to increase by 60% up to 2030.
According to the literature, cancer cells release different types of
extracellular vesicles that can travel through body ﬂuids such as
plasma, cerebrospinal ﬂuid, urine, breast milk, and exudates.
type of microvesicles called exosomes have been reported to be
involved in cancer progression.
Exosomes can act in a paracrine or endocrine manner to affect
the behavior of cells. A combination of speciﬁc exosomal cell
surface molecules is necessary for cell targeting, adhesion, and
Exosomes also may contain proteins that
were originally in the endosome membrane, such as annexins
and ﬂotilins. These proteins facilitate the transport and fusion of
exosomes with the membrane. Furthermore, tetraspanins are
involved in adhesion of the exovesicles with the target cell, like
other proteins such as Alix and TSG101.
Furthermore, exosomes derived from tumor cells seem to be
implicated in different processes such as tumor invasion, angio-
genesis, chemo-resistance, immune evasion, and cell death.
aspects suggest the importance of the study of exosomes and, in
our area of interest, their role in the development and progression
of CRC. Moreover, several studies have suggested that exosomes
could be useful as biomarkers and as drug carriers, in order to
achieve greater speciﬁcity and efﬁcacy of current therapies.
paper aims to review the actual knowledge of exosomes regarding
their nature, isolation, mechanisms of action, content, and
especially their role in CRC.
What are exosomes and how can they be
Exosomes are small vesicles enveloped by a lipid bilayer.
However, there is no consensus about the size of these particles.
Indeed, in the literature, variations in the deﬁnition of exosome
range from 30–100, 40–100, 50–150, to 40–200 nm.
tion, some authors call exosomes “communicasomes” because
they are involved in intercellular communication processes.
Journal of Gastroenterology and Hepatology 33 (2018) 792–799
© 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd