Microvesicles Derived From Mesenchymal Stem Cells Promote Human Renal Cancer Cell Growth And Aggressiveness Through Induction Of Hepatocyte Growth Factor

Aim:To investigate the effect and mechanism of micro-vesicles derived from humanWharton’s jelly mesenchymal stem cells (hWJMSC-MVs) on renal cancer cell(RCC).Methods:1. Human renal cancer cells(786-O)were co-cultured with MVs.786-O cells weredivided into three groups:1)+MV group;2)control group;3)RNase-MV group(MVs pre-treated with RNase), Analysis of CCK-8and cell cycle were used todetermine growth of tumor cells in vitro. Wound Healing Assay was alsoperformed to assess cell migration. Real-time PCR was performed to detect thegene expression of MMP-2and MMP–9in786-O cells.2. All nude mice received subcutaneous injection of1×107786-0cells to buildtransplantation tumor model. Animals were monitored every3days and recordedthe time-point of tumor occurrence. Tumor growth was evaluated by tumorvolume and tumor incidence. HGF,KI-67and Tunel staining were performed.3. Western blot analysis was used to detect the protein expression of MMP–2,MMP-9, cyclinD1,HGF,AKT and ERK1/2. In addition, we tested the protein expressions of p-ERK1/2、p-AKT in786-O cells after co-cultured with c-METinhibiter.conclusionMVs facilitate the growth and migration of786-0cells in vitro and vivo.MVinduced HGF expression and then accumulated the action of PI3k-AKT andRas/MAPK （ERK1/2） signal pathway may contribute to the proliferation andanti-apoptosis ability of786-O cells. Meanwhile, we found that MV could notpromote RCC growth after pre-treated by RNase, indicating that MVs might play arole through deliver effective nuclear acid (mRNA/miRNA) to target cells. MVsmight as a novel avenue for intercellular communication. This study also providedexperimental basis that HGF/c-MET signaling way may be one of RCC treatmenttargets.