1) Exosomes are extracellular vesicles smaller than 150 nm in diameter
composed of a lipid bilayer containing transmembrane proteins and enclosing
cytosolic proteins and RNA. Exosomes also contain surface molecules that allow
them to be targeted to recipient cells (Tkach et al. 2016).

The first time extracellular vesicles were described was only 35 years
ago, (pan et al 1983, harding et al 1984). It was only in 2010 that the
hypotheses of functional delivery of miRNA in exosomes to a target cell, was
demonstrated (Pegtel et al 2010). The field of exosomes is relatively new and
quickly evolving. While a lot of research is done, it is still difficult to
fully proof that certain hypothesis about exosomes are correct.

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By communication through functional delivery, exosomes play a role in
normal physiological and pathological processes (Lee et
al. 2012). An important pathological process where exosomes play a role is
tumor pathogenesis.

The last few years the role of tumor derived exosomes in tumor
progression and in tumor metastasis came forward in a lot of research. Metastasis
is the cause of most cancer death, furthermore the metastasis are often
difficult to target and treat (Hoye et al. 2016). This makes metastasis a big
problem and makes it really important to understand how cancer metastasize. With
the understanding how cancer metastasizes it could also be possible to come
closer to a way to prevent cancer from metastasizing and finding a treatment.
An important role of exosomes in metastasizing of cancer seems to be the
forming of the pre-metastatic niche. Therefore I think it is of great
importance to learn more about the role of exosomes in the forming of pre-
metastatic niche.

2) My research question is “What is the role of tumor derived exosomes in
the forming of pre-metastatic niche?”.
Furthermore, I would like to get insight in why some people get metastasis, why
tumors metastasize in some organs but not in other organs and what the role of
exosomes is in this. Also I would like to answer the question what the actual
proof is that exosomes play the role, that is assumed in the research, in the forming
of pre-metastatic niche because a lot of research is done in vitro or in vivo
in mice and it is difficult to actually proof it in vivo in humans. Also
considering how many different research groups have proved/detected the role of
exosomes in the formation of the pre-metastatic niche and if the prove or
assumptions are not mostly originating from one and the same research group.

If I am able to, I
would also like to get more insight in the possible treatments using the
information that is known about the role of exosomes in the forming of
premetastatic niche and possibly also get to know more about the barrier
function of macrophages in the forming of premetastatic niches by exosomes.


3) I will do a search in Pubmed, Embase and Cochrane using the same
advanced search. My search would be:


Exosom* [MESH]

niche [tiab]

Exosom* [tiab]

niche [tiab]

EV [tiab]

Premetast* OR
pre-metast* OR Metast* AND niche [tiab]

vesicle [tiab]


Total number of
articles pubmed:                         

Total number of
articles on pubmed:                      1019

Total combined on


Then I will take
out the duplicates and read the abstracts to exclude articles that are not
relevant. After that, I will read the remaining articles and exclude and/or include
articles again. I would exclude articles when they are not relevant for my
systematic review, for example when the main topic is not about metastatic
niches formed by exosomes or because it is not a type of article I could use
(like a systematic review). 


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