Expression of CXCL12 on pseudopalisading cells and proliferating microvessels in glioblastomas: An accelerated growth factor in glioblastomas

CXCL12, an α-chemokine that binds to G-protein-coupled CXCR4, plays an important and unique role in the regulation of stem/progenitor cell trafficking. To elucidate the correlation between the CXCR4/CXCL12 axis and glioblastomas (GBs), the present study assessed CXCR4/CXCL12 expression in 44 astrocytic tumor tissues using immunohistochemical analyses. Several cell lines of brain tumors were also analyzed by RT-PCR analyses. Although low-grade, astrocytic tumors were rarely positive for CXCL12 immunohistochemically, all GBs showed moderate to intense immunostaining with CXCL12, with particularly intense immunostaining being observed in the pseudopalisading cells and the proliferating microvessels. Regarding CXCR4, widespread positive immunoreactivity was noted in the tumor cells in almost all cases of GBs. In contrast, RT-PCR analysis showed low expression of CXCR4/CXCL12 in the aerophilic condition of GB cells and high expression of CXCR4/CXCL12 in the hypoxic condition of GB cells. Taken together, these results suggest that secretion of CXCR4/CXCL12 by hypoxic pseudopalisading and proliferating microvascular cells contributes to an outward migration of tumor cells away from hypoxia, creating a peripherally moving wave and subsequent microvascular proliferation. Pseudopalisades and proliferating microvessels are also considered to be associated with accelerated growth in GBs. These results indicate that expression of CXCL12 is an accelerated growth factor in GBs.