Placental mesenchymal stem cell-derived interleukin-6 promotes neuroblastoma progression

Neuroblastoma (NB) is a prevalent pediatric malignancy, yet the role of mesenchymal stem cells (MSCs) in NB progression remains unclear. MSCs are known to secrete various cytokines, including interleukin (IL)-6, and their influence on NB cells and tumor xenografts were investigated in this study. Placenta-derived mesenchymal stem cells (PMSCs) were isolated from chorionic villi and characterized via flow cytometry. The obtained PMSCs were co-cultured with NB cells or IL-6-silenced PMSCs. Comprehensive assays were conducted to assess proliferation, colony formation, cell cycle progression, apoptosis, migration, invasion, and epithelial-mesenchymal transition (EMT). RNA-seq identified differentially expressed genes (DEGs) in NB cells, predominantly enriched in Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways (P < 0.05). qRT-PCR revealed elevated levels of IL-6 and other oncogenic cytokines in PMSCs (P < 0.05). In vivo, IL-6 knockdown in PMSCs significantly suppressed NB xenograft growth, accompanied by reduced expression of Ki-67, proliferating cell nuclear antigen (PCNA), Caspase 9, and Snail as shown by immunohistochemistry (P < 0.05). Western blotting confirmed activation of phosphatidylinositol 3-kinases/protein kinase B (PI3K/AKT) pathway in NB cells after co-culture with PMSCs, which was attenuated by PI3K inhibition. Notably, IL-6 knockdown markedly suppressed NB xenograft progression and downregulated associated signaling markers (P < 0.05). Collectively, PMSC-derived IL-6 potentiates NB progression via PI3K-AKT signaling, presenting a potential therapeutic target in neuroblastoma.