CXCR4 enhances invasion and proliferation of bone marrow stem cells via PI3K/AKT/NF-κB signaling pathway

Osteosarcoma is the most common type of cancer that develops in bone, specifically; it is an aggressive malignant neoplasm. The purpose of this study is using superparamagnetic iron oxide nanoparticles (SPION) labeled bone mesenchymal stem cells (MSCs) to migrate into cancerous parts, then using alternating magnetic field to produce the high temperature to kill cancer cells in vitro. In order to enhance the invasion ability of MSCs, we successfully overexpressed CXCR4 in MSCs, we found the invasion behavior of CXCR4 overexpressed MSCs and CXCR4 overexpressed SPION labeled MSCs was enhanced when compared with MSCs. In addition, the proliferation of CXCR4 overexpressed MSCs and CXCR4 overexpressed SPION labeled MSCs. Then, we found that CXCR4 was able to enhance invasion related genes expression, including MMP9, MMP2, MMP13, MMP7, MMP10, MMP8, and MMP1. Among these genes, MMP9 and MMP2 were associated with PI3K/AKT/NF-κB signaling. The expression of MMP9 and MMP2 was decreased when PI3K/AKT signaling inhibitor LY294002 and NF-κB inhibitor PDTC were used respectively. Moreover the migrated of CXCR4 overexpressed MSCs and CXCR4 overexpressed SPION labeled MSCs were significantly reduced after LY294002 and PDTC used. These results suggest that CXCR4 overexpressed SPION labeled MSCs can be more easier migrate into cancerous parts; it may provide a promising method to treat the osteosarcoma.