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a a

b
b

Figure 7: Expression analysis of 4 overexpressed ex-miRNAs in MB cell lines CM
Figure 6: Expression analysis of 5 ex-miRNAs in MB cell lines CM and in CSF of and in CSF of MB patient. (a) TaqMan qRT-PCR analysis for miR-1290, miR-125a,
MB patient. (a) TaqMan qRT-PCR analysis for miR-486-3p, miR-572, miR-3918, miR-1298, miR-125b in CM of indicated cell lines; (b) TaqMan qRT-PCR analysis
miR-4476, miR-615 in CM of indicated cell lines; (b) TaqMan qRT-PCR for miR-1290, miR-125a, miR-1298 in MB-CSF (n = 3; ± standard deviation).
analysis for miR-572, miR-615 in MB-CSF (n = 3; ± standard deviation). MB: Medulloblastoma; CSF: Cerebral spinal fl uid; CM: Culture-medium; qRT-PCR:
MB: Medulloblastoma; CSF: Cerebral spinal fl uid; CM: Culture-medium; Quantitative reverse transcription polymerase chain reaction
qRT-PCR: Quantitative reverse transcription polymerase chain reaction
of multiple malignancies. [35-39] Consistently, detection
cancer stimulatory activities, thus contributing to the of metastasis-related ex-miRNAs in extracellular
formation of a pre-metastatic niche and promotion of environment of certain human malignancies, including
metastasis. [28,30] This exchange of miRNAs between breast and prostate cancers, were observed in other
primary tumors and target cells is an interesting studies. [40-44] Our observations provide indirect evidence
and novel dimension to the regulation of a cell supporting the hypothesis that ex-miRNA are
phenotype [31-34] and may be particularly important in possible facilitators of metastasis by modifying local
cancers that have a propensity for dissemination, such or distal microenvironments. [45] However, further
as MB. MB includes various subtypes with group 3 studies are needed using counter-regulation of key
and 4 subtypes being clinically distinct with regard ex-miRNA expression to determine their effect on
to metastasis and prognosis, which may also manifest regulation of motility, migration, and invasion of MB
in a difference in their miRNA spectra. Hence, it was cells.
not surprising to fi nd a group of miRNAs that were
uniquely over-(60 miRNAs) or under-represented (52 To the best of our knowledge, this is the fi rst study
miRNAs) in the CM of the 2 metastasis-related cell revealing the spectra of ex-miRNAs in cell CM
lines D283 and D341. More importantly, we identifi ed 4 conditioned by MB cell lines and in CSF of an MB
miRNAs (miR-1290, miR-125a, miR-125b, miR-1298) patient. Although the number of samples studied here is
that were over-represented in MB CSF and signifi cantly very small, our identifi cation of key secreted miRNAs
enriched in the CM media of the 2 metastasis-related that are specifi cally enriched in MB-CSF provides a
cell lines (D283 and D341). Remarkably, apart rationale for future investigations. Such investigations,
from miR-1298, where no functional information is using larger sets of MB samples could lead in the
publically available, the 3 other miRNAs (miR-1290, near future to the discovery of CSF-derived miRNA
miR-125a, miR-125b) were detected in body fl uids markers, with diagnostic and prognostic signifi cance
of various cancer patients, whereby their increased and ultimately, hopefully also with therapeutic
expression and/or secretion is associated with metastasis potential.

Journal of Cancer Metastasis and Treatment ¦ Volume 1 ¦ Issue 2 ¦ July 15, 2015 ¦ 73