Extracellular vesicles: Toward a clinical application in urological
and Takahiro Ochiya
Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, and
Department of Urology, Jikei
University School of Medicine, Tokyo, Japan
Abbreviations & Acronyms
AR-V7 = androgen receptor splice
BCa = bladder cancer
CRPC = castration-resistant
Dex = dendritic cell derived
EDIL-3 = epidermal growth
factor-like repeats and discoidin
EV = extracellular vesicle
HUVEC = human umbilical vein
lncARSR = long non-coding
ribonucleic acid activated in renal
cell carcinoma with sunitinib
lncRNA = long non-coding
miRNA = micro ribonucleic acid
mRNA = messenger ribonucleic
MVB = multivesiclular body
nSMase2 = neutral
PCa = prostate cancer
PD-1 = programmed death 1
PD-L1 = programmed death 1
RCC = renal cell carcinoma
siRNA = small interfering
TACSTD2 = tumor-associated
calcium-signal transducer 2
Correspondence: Takahiro Ochiya
Ph.D., Division of Molecular and
Cellular Medicine, National Cancer
Center Research Institute, 5-1-1
Tsukiji, Chuo-ku, Tokyo 104-0045,
Japan. Email: firstname.lastname@example.org
Received 24 January 2018; accepted
26 March 2018.
Online publication 3 May 2018
Abstract: Extracellular vesicles are nanometer-sized lipid membranous vesicles that are
released from almost all types of cells into the extracellular space. Extracellular vesicles
have gained considerable attention in the past decade, and emerging evidence suggests
that they play novel roles in mediating cancer biology. Extracellular vesicles contain
pathogenic components, such as proteins, DNA fragments, messenger ribonucleic acids,
non-coding ribonucleic acids and lipids, all of which mediate paracrine signaling in the
tumor microenvironment. Extracellular vesicles impact the multistep process of cancer
progression through modulation of the immune system, angiogenesis and pre-metastatic
niche formation through transfer of their contents. Therefore, a better understanding of
their roles in urological cancers will provide opportunities for novel therapeutic
strategies. In addition, the contents of extracellular vesicles hold promise for the
discovery of liquid-based biomarkers for prostate, kidney and bladder cancers. Here, we
summarize the current research regarding extracellular vesicles in urological cancer and
discuss potential clinical applications for extracellular vesicles in urological cancer.
clinical application, exosome, extracellular vesicles, urological cancer.
EVs consist of a wide variety of small membrane-bound vesicles, including exosomes and
microvesicles, which are actively released from almost all types of cells.
Initially, it was
shown that the release of EVs was part of a disposal process to discard unwanted materials
In 2007, Jan L
otvall’s group showed that variable RNA, such as miRNA and
mRNA, can be transferred between cells through EVs.
In 2010, three research groups
reported that these transferred miRNAs were able to function within the recipient cells.
Since then, emerging evidence has shown that EVs are important mediators of extracellular
signaling pathways through transfer of their cargo. Depending on the cell origin, EV content
varies greatly. EVs transfer functional molecules, including miRNAs, mRNAs, proteins, DNA
fragments and lipids, into recipient cells. Through the transfer of these contents, EVs have
been reported not only to function in normal physiological processes,
but also to be associ-
ated with the pathogenesis of various diseases, including cancer.
shows that EVs play decisive roles in tumorigenesis, growth, progression, metastasis and drug
In addition, EVs reﬂect the phenotypes of parental cells, and many reports have
shown their usefulness as diagnostic or prognostic biomarkers.
Furthermore, the concept of
using EVs for siRNA delivery based on the discovery of miRNA transfer is also an important
aspect of EV research.
In the present review, we provide a brief introduction to EVs, summarize the current
knowledge on EVs in the urological cancer ﬁeld and discuss potential clinical applications for
the near future.
Biogenesis of EVs
EVs are often categorized as exosomes, microvesicles, and apoptotic bodies based on their
size and secretory origins.
Exosomes are small bilayered EVs that range from 50 to 100 nm
in diameter, and are derived from the intracellular endosomal component.
Exosomes are ini-
tially formed by inward budding from the limiting membrane of late endosomes, resulting in
© 2018 The Japanese Urological Association
International Journal of Urology (2018) 25, 533--543 doi: 10.1111/iju.13594