Affiliations: [a] Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran | [b] Department of Biology, Faculty of Science, University of Isfahan, Isfahan, Iran | [c] Pathology Laboratory, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
Abstract: BACKGROUND: miRNAs have recently been implicated in tumor's microenvironment remodeling
and tumor-stromal cells interactions. We have previously reported a
signaling role for miR-21, as a secretory molecule released by cancer
associated fibroblasts (CAF) adjacent to esophagus tumor cells. OBJECTIVE: To discover other potential signaling miRNAs, we employed a co-culture
system of esophageal cancer cell line and normal fibroblasts to mimic the
tumor microenvironment. METHODS: We measured the expression profile of secretory miRNAs in the conditioned
media (CM) of our co-culture system using a panel PCR array. We used pathway
enrichment analysis to define potential pathways regulated by these miRNAs.
Then using ultracentrifugation, we purified exosomes secreted to the CM of
co-cultured cell lines and evaluated exosomal secretion of these miRNAs. RESULTS: We found 18 miRNAs which were significantly up/down-regulated in the CM of
co-culture system. Pathways related to cell adhesion, endocytosis and cell
junctions were among the enriched pathways that might be related to CAF
phenotype and tumor progression. Moreover, we detected higher exosomal
levels of miR-33a and miR-326 in the purified exosomes both in co-cultured
and untreated CM. So, these miRNAs are mainly secreted into the CM by means
of exosomes. CONCLUSIONS: Briefly, our data shed more light on the role of CAFs through secretion of
miRNAs within tumor microenvironment and propose novel therapeutic targets
for esophageal and probably other cancer types.
