JOURNAL OF BIOLOGICAL REGULATORS & HOMEOSTATIC AGENTS Vol. 33, no. 5, 1451-1463 (2019)
Brain gliomas and growth factors: immunohistochemical, immunofluorescence, flow cytometry and RT-PCR profile in pediatric age.
- 1 Department of Sensory Organs, “Sapienza” University of Rome, Rome, Italy.
- 2 Department of Anatomy, Histology, Forensic Medicine and Orthopedics, “Sapienza” University of Rome, Rome, Italy.
- 3 Department of Medical-Surgical Sciences and Biotechnologies,”Sapienza” University of Rome, Rome, Italy.
- 4 Department of Radiology, Oncology and Pathology, “Sapienza” University of Rome, Rome, Italy.
- 5 Department of Biochemical Sciences “A. Rossi Fanelli”, “Sapienza” University of Rome, Rome, Italy.
- 6 IRCCS Neuromed, Pozzilli (Is), Italy.
- 7 Department of Systems Medicine, “Tor Vergata” University of Rome, Rome, Italy.
- 8 Department of Experimental Medicine, “Sapienza” University of Rome, Rome, Italy.
- 9 Department of Biomolecular Sciences, University of Urbino “Carlo Bo”, Urbino, Italy.
- 10 Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy.
- # Contributed equally
Gliomas represent over 50% of tumors occurring in children. Evidence suggests that glioma stem cells (GSCs), maintained by the transforming growth factor-beta (TGF-β1) pathway, and vascularization substantially contribute to tumor aggressiveness. The identification of important angiogenic factors such as vascular endothelial growth factor (VEGF) may represent a crucial step in the therapeutic approach against tumor growth and metastatic diffusion. The aim of this study was to identify the expression of TGF-β1, VEGF and VEGF-receptors in brain gliomas. Specimens of 16 gliomas and 4 controls from children aged 0.2-14 years were used in the study. Immunohistochemical analysis and gene expression study from specimens was performed. Flow cytometry analysis on GSCs was performed to ascertain the expression of VEGF and VEGF-R2 in the tumor stem cell compartment. Newly diagnosed gliomas mainly showed moderate to strong VEGF immunostaining and increased expression of pro-inflammatory molecules in glioma cells. The proportion of TGF-β1 positive endothelial cells was markedly lower in normal brain vessels compared to tumor vessels. These findings demonstrate that the glioma mass is constituted by a phenotypically immature anoxic central area with a proliferating hypoxic layer; the peripheral area is characterized by cell types with a higher degree of differentiation expressing pro-angiogenic factors. Our data have proven that GSCs play a central role in promoting glioma neovascularization. These findings are useful to understand glioma vascularization, have relevant implications in the therapeutic options and may favor new insights into stem cells biology and suggest therapeutic opportunities for the anti-vascular treatment strategy.
IHC, RT-PCR, angiogenesis, brain gliomas, childhood cancers, growth factors
- Journal Article