Rat Bone Marrow-Derived Mesenchymal Stem Cells Promote the Migration and Invasion of Colorectal Cancer Stem Cells

大鼠骨髓间充质干细胞促进结直肠癌干细胞的迁移和侵袭

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Abstract

BACKGROUND: Colorectal cancer is one of the most common cancers and the second leading cause of cancer-related deaths worldwide. Targeting cancer stem cells (CSCs) may be a novel strategy for the treatment of colorectal cancer. Previous studies have shown that bone marrow-derived MSCs (BM-MSCs) promote tumor growth and metastasis. However, the role of rat BM-MSCs in the biological behaviors of colorectal CSCs remains unclear until now. MATERIALS AND METHODS: BM-MSCs were isolated from rats and characterized. CSCs were enriched from HCT116 cells using the microsphere culture method, and the microspheres incubated for at least 10 passages were termed HCT116-CSCs that were characterized. The effects of rat BM-MSCs on migration and invasion of HCT116-CSCs were examined using transwell migration and invasion assays and xenograft tumor growth assay. RESULTS: Rat BM-MSCs appeared typical stem cell morphology. Flow cytometry revealed positive CD29 and CD44 expression in rat BM-MSCs at passage 3, and rat BM-MSCs were found to differentiate into osteocytes following incubation in osteogenic induction medium. Microscopy, flow cytometric detection of stem cell surface markers, colony-formation assay and transwell migration and invasion assays characterized the successful preparation of HCT116-CSCs, and subcutaneous injection of HCT116-CSCs produced xenograft tumors in nude mice, while HE staining of the xenograft tumors displayed cancer specimen shapes. Transwell migration and invasion assays showed that rat BM-MSCs promoted the migration and invasion of HCT116-CSCs, and injection of rat BM-MSCs was found to promote the growth of the mouse xenograft tumor derived from HCT116-CSCs. CONCLUSION: Rat BM-MSCs promote the migration and invasion of colorectal CSCs, and colorectal CSCs may be a potential target for the therapy against colorectal cancer.

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