Glioblastoma multiforme (GBM) is essentially untreatable because portions of the tumor invading normal brain are inaccessible to conventional therapies. Neural stem cells (NSCs) are intrinsically attracted to tumor sites in the brain, and have the potential to act as vehicles to deliver therapeutic agents to these otherwise inaccessible cancer cells. In glioma, NSCs are found in close contact with tumor cells, raising the possibility that NSC may preferentially form contacts with glioma tumor cells and not other types of cells. To better understand the mechanisms underlying NSC interactions with glioma cells, we examined NSC-target cell contacts in a highly simplified 3-dimensional peptide hydrogel (Puramatrix) in which cell behaviors can be studied in the relative absence of external cues. HB1.F3 is an immortalized clonal human NSC line extensively characterized in preclinical investigations.

Using high-resolution confocal microscopy, NSCs were observed contacting or encircling glioma cells, but never the reverse. Next, examining specificity of these contacts, no significant differences in either percentages of NSCs contacting targets, or in the extent of target cell encirclement, were observed when NSCs were presented with various potential target cells (human glioma and breast cancer cell lines, patient-derived brain tumor lines, non-tumor fibroblasts, primary mouse and human astroglial cells, and primary adult and newborn human dermal fibroblasts) except that interactions between NSCs cells did not progress beyond establishing contacts. We conclude that formation of contacts and subsequent encirclement of target cells by NSCs is an intrinsic property, and that preferential contact formation with tumor cells in vivo must therefore be highly dependent on the microenvironment and cues originating in the and interface between tumor and brain.