The CXCL16–CXCR6 chemokine axis in glial tumors

• The chemokine CXCL16 is heavily expressed by astrocytoma cells.
• Its receptor CXCR6 is expressed only on a small subpopulation of tumor cells.
• CXCR6 tumor cells co-stain for markers of embryonic and neural stem cells.
• Almost all CXCR6-positive cells are positive for Mushasi.
• About half of Oct4-, Sox2- or Nanog-positive cells stain for CXCR6.

Since chemokines and their receptors play a pivotal role in tumors, we investigated the CXCL16–CXCR6-axis in human astroglial tumors. The transmembrane chemokine CXCL16 is heavily expressed by tumor, microglial and endothelial cells in situ and in vitro. In contrast, the receptor CXCR6 is restricted in glioblastomas to a small subset of proliferating cells positive for the stem-cell markers Musashi, Nanog, Sox2 and Oct4. In particular, the vast majority (about 90%) of Musashi-positive cells stained also for CXCR6. Thus, CXCL16 is highly expressed by glial tumor and stroma cells whereas CXCR6 defines a subset of cells with stem cell character.