OncoTargets and Therapy (Jul 2020)
Rat Bone Marrow-Derived Mesenchymal Stem Cells Promote the Migration and Invasion of Colorectal Cancer Stem Cells
Abstract
Weiyan Zou,1 Jie Zhao,2 Yi Li,2 Zishu Wang,3 Haiqin Yan,1 Yudong Liu,1 Meiqun Sun,1 Jialu Zhuang,2 Junbin Wang3 1Department of Histology and Embryology, Bengbu Medical College, Bengbu 233004, Anhui Province, People’s Republic of China; 2The Second School of Clinical Medicine, Bengbu Medical College, Bengbu 233004, Anhui Province, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, Anhui Province, People’s Republic of ChinaCorrespondence: Junbin Wang Email [email protected]: 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.Keywords: bone marrow-derived mesenchymal stem cells, colorectal cancer, cancer stem cells, migration, invasion
