Overexpression of CXC chemokine receptors is required for the superior glioma-tracking property of umbilical cord blood-derived mesenchymal stem cells.

Our observations indicate that umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) have a strong migration capacity toward the human glioma cell line, U-87 MG, LN18, U138, and U251, when compared to several other cancer cell lines. In order to identify soluble factors that function to attract UCB-MSCs, we used cytokine antibody arrays to screen changed cytokines in conditioned media from U-87 MG cells. Among these, interleukin-8 (IL-8) and growth-related oncogene (GRO-alpha) enhanced UCB-MSC migration. Furthermore, antibodies treatment against the IL-8 receptors reduced these migration events and overexpression of IL-8 in cells with lower level of IL-8 such as A549 could induce UCB-MSC migration. Since we found that the capacity of UCB-MSC migration is much higher than that of bone marrow-derived MSCs (BM-MSCs) toward either U-87 MG cells or recombinant IL-8, we compared the levels of the IL-8 receptor, CXC chemokine receptor 1 (CXCR1) and CXCR2 between two kinds of MSCs by RT-PCR and immunostaining. Expression levels of two receptors were much higher in UCB-MSCs than in BM-MSCs. These data suggest that higher levels of two IL-8 receptors could influence downstream signaling events affecting superior UCB-MSC migration toward the glioma cells.