Mesenchymal stem cells accelerated growth and metastasis of neuroblastoma and preferentially homed towards both primary and metastatic loci in orthotopic neuroblastoma model

Background: Majority of neuroblastoma patients develop metastatic disease at diagnosis and their prognosis is poor with current therapeutic approach. Major challenges are how to tackle the mechanisms responsible for tumorigenesis and metastasis. Human mesenchymal stem cells (hMSCs) may be actively involved in the constitution of cancer microenvironment. Methods: : In our study, an orthotopic neuroblastoma murine model was utilized to mimic the actual scenario. Human neuroblastoma cell line SK-N-LP was transfected with luciferase gene, which were inoculated with/without MSCs into the adrenal area of SCID-beige mice. The growth and metastasis of neuroblastoma was observed by using Xenogen IVIS 100 in vivo imaging and evaluating gross tumors ex vivo . The homing of MSCs towards tumor was analyzed by tracing fluorescence signal tagged on MSCs using CRI Maestro TM imaging system. Results: : hMSCs mixed with neuroblastoma cells significantly accelerated tumor growth and metastasis of neuroblastoma in vivo . hMSCs could be recruited by primary tumor and also become part of the tumor microenvironment in the metastatic lesion. The metastatic potential was significantly reduced when hMSCs were pre-treated with stromal cell derived factor-1 (SDF-1) blocker, AMD3100, suggesting that the SDF-1/CXCR4 axis was a prime mover in the metastatic process. Conclusions: : MSCs accelerated and facilitated tumor formation, growth and metastasis. Furthermore, the homing propensity of MSCs towards both primary tumor and metastatic loci can also provide new therapeutic insights in utilizing bio-engineered MSCs as vehicles for targeted anti-cancer therapy against advanced cancers.