gms | German Medical Science

Objective: PRG5 represents a brain-specific integral membrane protein which is involved in neurite-retraction, endocytosis, transcription and transformation by altering the RhoA and ROCK pathway. In malignant glioma positive expression pf PRG 5 has been demonstrated in clinical data, however the biological function of PRG5 in malignant glioma remains unknown. It was the aim of this experimental study to investigate the role of PRG5 for glioma growth and angiogenesis and to investigate ist influence on antiangiogenic therapy.

Method: Knock-out (KO) of PRG5 in GL261 glioma cells was induced using siRNA. Tumor cells were injected into the brain of Bl6 mice (10.000 cell per animal) using a stereotactic approach. MRI was performed on days 7, 14, 21, 28 and 35 after injection. Tumor cells were implanted into the cranial window model in Bl6 animals and tumor angiogenesis was analysed using fluorescent intravital microscopy (IVM) on days 8, 11 and 14 after implantation. Sunitinib treatment (80mg per kg body weight) was applied ip when tumors reached a volume of 3 mm³ for MR imaging or 8 days after tumor cell implantation for IVM analysis.

Results: PRG5 KO induced a significant delay in tumor growth (Control: day 21: 17 ± 9 mm³ vs. PRG KO: day 21: 2,6 ± 1,3 mm³). Sunitinib treatment did not alter tumor growth in PRG5 KO tumors. Total vessel density did not differ between control and PRG5 KO tumors. Sunitinib treatment did not reduce vascular density in PRG5 KO tumors compared to PRG5 KO tumors receiving placebo treatment (Vessel density: Placebo: 171 ± 12 cm/cm² vs Sunitinib: 142 ± 9 cm/cm²).

Conclusions: Knock down of PRG5 in glioma cells leads to delayed tumor growth and resistance to antiangiogenic therapy in a preclinical orthotopic glioma model.