Glioma stem-like cells can be targeted in boron neutron capture therapy with boronophenylalanine

Authors:   Natsuko Kondo,Masaki Hikida,Mitsutoshi Nakada,Yoshinori Sakurai,Eishu Hirata,Satoshi Takeno,Minoru Suzuki
Journal: Cancers
https://doi.org/10.3390/cancers12103040
Abstract: As glioma stem cells are chemo-and radio-resistant, they could be the origins of recurrent malignant glioma. Boron neutron capture therapy (BNCT) is a tumor-selective particle radiation therapy.10 B(n,$alpha$)7 Li capture reaction produces alpha particles whose short paths (5–9 µm) lead to selective killing of tumor cells. P-boronophenylalanine (BPA) is a chemical compound used in clinical trials for BNCT. Here, we used mass cytometry (Cytof) to investigate whether glioma stem-like cells (GSLCs) take up BPA or not. We used GSLCs, and cells differentiated from GSLCs (DCs) by fetal bovine serum. After exposure to BPA for 24 h at 25 ppm in 5% CO2 incubator, we immune-stained them with twenty stem cell markers, anti-Ki-67, anti-BPA and anti-CD98 (heterodimer that forms the large BPA transporter) antibodies and analyzed them with Cytof. The percentage of BPA+ or CD98+ cells with stem cell markers (Oct3/4, Nestin, SOX2, Musashi-1, PDGFR$alpha$, Notch2, Nanog, STAT3 and C-myc, among others) was 2–4 times larger among GSLCs than among DCs. Analyses of in vivo orthotopic tumor also indicated that 100% of SOX2+ or Nestin+ GSLCs were BPA+, whereas only 36.9% of glial fibrillary acidic protein (GFAP)+ DCs were BPA+ . Therefore, GSLCs may take up BPA and could be targeted by BNCT.