1) tumor progression and in tumor metastasis came forward

1) Exosomes are extracellular vesicles smaller than 150 nm in diametercomposed of a lipid bilayer containing transmembrane proteins and enclosingcytosolic proteins and RNA. Exosomes also contain surface molecules that allowthem to be targeted to recipient cells (Tkach et al. 2016).The first time extracellular vesicles were described was only 35 yearsago, (pan et al 1983, harding et al 1984). It was only in 2010 that thehypotheses of functional delivery of miRNA in exosomes to a target cell, wasdemonstrated (Pegtel et al 2010). The field of exosomes is relatively new andquickly evolving. While a lot of research is done, it is still difficult tofully prove that certain hypothesis about exosomes are correct.By communication through functional delivery, exosomes play a role innormal physiological and pathological processes (Lee etal.

2012). An important pathological process where exosomes play a role istumor pathogenesis. The last few years the role of tumor derived exosomes in tumorprogression and in tumor metastasis came forward in a lot of research. Metastasisis the cause of most cancer death, furthermore the metastasis are oftendifficult to target and treat (Hoye et al. 2016).

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This makes metastasis a bigproblem and makes it really important to understand how cancer metastasize. Withthe understanding how cancer metastasizes it could also be possible to comecloser to a way to prevent cancer from metastasizing and finding a treatment.An important role of exosomes in metastasizing of cancer seems to be theforming of the pre-metastatic niche.

Therefore I think it is of greatimportance 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 inthe forming of pre-metastatic niche?”. Furthermore, I would like to get insight in why some people get metastasis, whytumors metastasize in some organs but not in other organs and what the role ofexosomes is in this.

Also I would like to answer the question what the actualproof is that exosomes play the role, that is assumed in the research, in the formingof pre-metastatic niche because a lot of research is done in vitro or in vivoin mice and it is difficult to actually prove it in vivo in humans. Alsoconsidering how many different research groups have proved/detected the role ofexosomes in the formation of the pre-metastatic niche and if the prove orassumptions are not mostly originating from one and the same research group.If I am able to, Iwould also like to get more insight in the possible treatments using theinformation that is known about the role of exosomes in the forming ofpremetastatic niche and possibly also get to know more about the barrierfunction of macrophages in the forming of premetastatic niches by exosomes.I think that I will find out that exosomes have an important role inthe forming of the pre-metastatic niche, however I do think that this is aconcept that is difficult to fully prove and is not yet irrefutable proved.

3) I will do a search in Pubmed, Embase and Cochrane using the sameadvanced search. My search would be:  Exosom* MESH Pre-metastatic niche tiab Exosom* tiab Premetastatic niche tiab EV tiab Premetast* OR pre-metast* OR Metast* AND niche tiab Extracellular vesicle tiab   Total number of articles pubmed:                          28739 Total number of articles on pubmed:                      1019 Total number of articles combined on pubmed:                     113  Then I will takeout the duplicates and read the abstracts to exclude articles that are notrelevant. After that, I will read the remaining articles and exclude and/or includearticles again. I would exclude articles when they are not relevant for mysystematic review, for example when the main topic is not about metastaticniches formed by exosomes or because it is not a type of article I could use(like a systematic review).