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Schulze et al. J Cancer Metastasis Treat 2020;6:42 I http://dx.doi.org/10.20517/2394-4722.2020.79 Page 3 of 10

Figure 1. Dual role of exosomes in cancer progression. Cancer cell-derived exosomes contribute to the formation of the pre-metastatic
microenvironment, tumor growth and progression, immune escape, angiogenesis, anti-apoptotic signaling, drug-resistance, and so on.
While exosomes from healthy cells including dendritic cells, B cells, and T cells, play crucial role in inhibiting tumor growth (This figure
was created with BioRender.com)

[78]
derived exosomes synthesis, release, and uptake may serve as an effective cancer therapy . With the use
[78]
of a mouse model, Bobrie et al. found that blockade of Rab27a, a key mediator of exosome secretion,
resulted in decreased primary tumor growth and lung dissemination of metastatic carcinoma (4T1) cells.
It was found that miR‐494 is enriched in melanoma‐derived exosomes, and that exosomal transport of
[79]
miR‐494 promotes metastasis . More specifically, inhibiting the function of Rab27a blocked exosomal
[79]
transfer of miR-494 and resulted in inhibiting melanoma growth and metastasis . Another possible way
to mitigate tumor growth is to simple remove circulating exosomes via a hemofiltration system (such as the
TM
Aethlon ADAPT system). This alternative may also serve as another possible therapeutic approach for
[80]
reversing immune dysfunction and improving the immune responses to tumor growth . Finally, multiple
studies have discovered that blocking exosomal uptake is another potentially effective method for cancer
therapy [81,82] . For example, the heparan sulfate (HS) proteoglycans has been discovered as internalizing
[82]
receptors of cancer cell-derived exosomes . HSPG deficiency, or the HS mimetic (heparin) treatment,
[82]
significantly reduced exosome uptake and exosome-mediated stimulation of cancer cell migration . In all
three cases (blocking exosomal secretion, exosomal removal, and blocking exosomal uptake), disrupting