Abstract
Objective : At present, human bone marrow mesenchymal stem cells
(hBMSCs) used as target vectors for hypopharyngeal cancer is a new
therapeutic direction of great potential. However, hBMSCs would be
transmitted into cancer-associated fibroblasts (CAFs) under the
induction of hypopharyngeal cancer. Here, we aimed to determine whether
microRNA-21(miR-21) in exosomes from FaDu cells would play a role in
hypopharyngeal cancer induced transition of hBMSCs to CAFs.
Methods : qRT-PCR and western blot were employed to investigate
expression level of miR-21 in hypopharyngeal cancer patient samples and
FaDu cells. The exosomes were collected from FaDu cells then isolated
and identified. Cell morphological changes were observed by inverted
phase contrast microscope. Expression level of CAF-related proteins,
includingα-SMA and FAP, were assessed by qRT-PCR and western blot.
Cell cycle of hBMSCs were determined by flow cytometry.
Results : MiR-21 expression level was up-regulated in
hypopharyngeal cancer tissue and FaDu cells. Exosomes from FaDu cells
promoted CAFs-like features of hBMSCs, including up-regulation of α-SMA
and FAP and cell morphological changes. Proportions of hMBSCs in G1
phase significantly decreased, while proportions of hMBSCs in G2 phase
significantly decreased at the presence of exosomes from FaDu cells.
What’s more, miR-21 knock-out in FaDu cells suppressed transition of
bone marrow mesenchymal stem cells to cancer-associated fibroblasts and
reversed the cell cycle change.
Conclusions : Our data showed that miR-21 promotes
hypopharyngeal cancer induced transition of bone marrow mesenchymal stem
cells to cancer-associated fibroblasts.
Keywords : Hypopharyngeal cancer, Bone marrow mesenchymal stem
cells, Cancer-associated fibroblasts, MicroRNA-21, Exosomes