Journal Article

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

Chan, Shing, Fung, Marcus Kwong-Lam, Chan, Godfrey Chi-Fung, Yu, Jiao-Le

2021

Overview

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 An orthotopic neuroblastoma murine model was utilized to mimic the clinical scenario. Human neuroblastoma cell line SK-N-LP was transfected with luciferase gene, which were inoculated with/without hMSCs 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 hMSCs towards tumor was analyzed by tracing fluorescence signal tagged on hMSCs using CRI Maestro™ imaging system. Results hMSCs mixed with neuroblastoma cells significantly accelerated tumor growth and apparently enhanced 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 consistently reduced in lung and tumor when hMSCs were pre-treated with stromal cell derived factor-1 (SDF-1) blocker, AMD3100, suggesting that the SDF-1/CXCR4 axis was one of the prime movers in the metastatic process. Conclusions hMSCs accelerated and facilitated tumor formation, growth and metastasis. Furthermore, the homing propensity of hMSCs towards both primary tumor and metastatic loci can also provide new therapeutic insights in utilizing bio-engineered hMSCs as vehicles for targeted anti-cancer therapy.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Animal models / Animals / Biomedical and Life Sciences / Biomedicine / Bone cancer / Bone marrow / Cancer / Cancer Research / Cell and molecular biology / Cell Communication / Cell Line, Tumor / Cell Proliferation / Committees / CXCR4 protein / Development and progression / Disease Models, Animal / Gene Expression / Genes, Reporter / Growth / Health aspects / Health Promotion and Disease Prevention / Heterografts / Homing / Humans / Laboratory animals / Medical prognosis / Medicine/Public Health / Mesenchymal Stem Cell Transplantation / Mesenchymal stem cells / Mesenchymal Stem Cells - metabolism / Metastases / Metastasis / Mice / Mice, SCID / Neoplastic Processes / Neuroblastoma / Neuroblastoma - etiology / Neuroblastoma - metabolism / Neuroblastoma - pathology / Neuroblastoma cells / Oncology / Receptors, CXCR4 - metabolism / Research Article / SDF-1 protein / Stem cell transplantation / Stem cells / Surgery / Surgical Oncology / Transplants & implants / Tumor Burden / Tumor Microenvironment / Tumorigenesis / Tumors