MCP-1/CCR2 axis promotes the homing of human umbilical cord mesenchymal stem cells to lung cancer tissues
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Abstract:
Objective:To study the role of monocyte chemoatractant protein-1 (MCP-1)/(chemokine \[C-C motif\] receptor 2, CCR2) axis in human umbilical cord mesenchymal stem cells(HUMSCs) homing to lung cancer. Methods: “Tissue explant” method was used to isolate and identify HUMSCs from umbilical cord of healthy newborns. Subcutaneous lung cancer xenograft model was established in nude BALB/c mice. Transwell migration assay in vitro and IVIS Xenogen living imaging system in vivo were applied respectively to investigate the capability of HUMSCs homing to lung cancer. ELISA was utilized to detect the secretion of monocyte chemoatrractant protein-1(MCP-1)in lung cancer A549 cell culture supernatant. After knocking down the MCP-1 expression in lung cancer cells by transfecting shRNA and blocking MCP-1 receptor CCR2 on the surface of HUMSCs by inhibitor RS504393, the migration ability of HUMSCs was determined in vitro and in vivo. Results: HUMSCs were successfully isolated and identified. Subcutaneous lung cancer xenograft model was successfully established in nude BALB/c mice. HUMSCs migrated to lung cancer both in vivo and in vitro(P<0.01). Lung cancer cells highly expressed MCP-1. Lung cancer A549 cell line with stable low expression of MCP-1 was successfully constructed, compared with control group, number of migrating HUMSCs significantly decreased in shRNA1 and shRNA2 knock down groups (\[80.0±33.0\],\[94.0±16.0\] vs \[167.0±41.0\],P<0.05). Inhibition of CCR2 (receptor of MCP-1) on HUMSCs greatly suppressed the tropism of HUMSCs to lung cancer in vivo and in vitro (P<0.05). Conclusion: MCP-1/CCR2 axis promoted the migration of HUMSCs to lung cancer.
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Project supported by the National Basic Research Program of China(973 Program)(No. 2012CB9333004),the National Key Technology R & D Program(No. 2015BAI12B12),the National Natural Science Foundation of China(No. 81401887),Applied Basic Research Programs of Science and Technology Commission Foundation of Tianjin City (No. 14JCQNJC11500, No. 11JCYBJC13200), and the Science Foundation of Tianjin Medical University(No. 2012KYM03)