Poster Presentation Advances in Neuroblastoma Research Congress 2016

Modulation of immune responses and radioresistance by neuroblastoma-derived and host-derived TrkB-target Galectin-1 (#348)

Katharina Batzke 1 , Gabriele Büchel 2 , Alexander Schramm 1 , Johannes Schulte , Wiebke Hansen 1
  1. University Hospital Essen, Bottrop, NORTH RHINE WESTPHALIA, Germany
  2. University of Würzburg, Würzburg, Germany

Chemotherapy and external beam radiation constitute the backbone therapy of high-risk neuroblastoma, suggesting that analyses of response modulators could be useful. TrkB expression has been linked to chemoresistance before, but response to radiotherapy has been less well explored. We previously identified the multifunctional protein Galectin-1 (Gal-1) as a target of TrkB to promote angiogenesis and invasiveness. In order to elucidate the contribution of Gal-1 to tumour formation and tumour-host interaction, we crossbred TH-MYCN mice with Gal-1 knock-out mice. Gal-1 gene dosage did not significantly alter tumour incidence, but reduced Gal-1 gene dosage correlated with impaired tumour angiogenesis, splenomegaly and impaired T cell tumour infiltration.
Interestingly, Gal-1 deficient CD4+ T cells presented with a lower migratory capacity towards tumour cells in vitro. As TrkB and Gal-1 have also been described as targets of ionizing radiation, we further explored their role in neuroblastoma cells in vitro. Upregulation of TrkB and Gal-1 was observed upon ionizing irradiation by qPCR and Western Blot analyses. However, colony formation assays of irradiated cells did not reveal altered cell survival of murine neuroblastoma cell lines when Gal-1 was down-regulated using Gal-1 specific shRNAs. The effect of abrogating Gal-1 and TrkB functions on the radiation response remains to be explored in vivo by using small molecule inhibitors and shRNAs, respectively. These results are expected to reveal the role for the TrkB/Gal-1 axis in response to radiation and to contribute to a better understanding of the complex tumour-host interaction during chemo- and radiotherapy of neuroblastoma.