Some growth factors in neoplastic tissues of brain tumors of different histological structure

Abstract

Introduction. Pathologic angiogenesis is typical for angiogenic diseases including tumor growth. Vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), transforming growth factor alpha and beta (which are also known as “triggers” of angiogenesis), and other factors (Gacche, Meshram, 2013; Nijaguna et al., 2015) play a special role in its development. Evaluation of the important mechanisms of angiogenesis in physiological and pathological conditions remains to be a subject of heightened interest for the past 30 years. It is known that VEGF A is the main trigger of growing blood vessels into the tumor tissue. This is specific mitogen signal for endothelial cells that triggers the mechanisms of cell division and migration. VEGF-induced tumor vasculature has a number of structural and functional features that provide growth and progression of tumors, including increased permeability of blood vessels and their chaotic arrangement. Objective: to study in comparative aspect the level of certain growth factors in the following tissues: glioblastomas, brain metastasis of the breast cancer, meningiomas as well as corresponding peritumoral areas. Materials and methods. Tissue samples were obtained from 56 patients admitted to the surgical treatment in Rostov Research Institute of Oncology: 24 patients had glioblastomas, 19 patients had brain metastasis of the breast cancer, 13 patients with meningiomas without peritumoral edema. Histological control was carried out in all cases. Age of patients ranged from 35 to 72 years. The level of growth factor was detected in the samples of tumor tissue and regions immediately adjacent to the tumor foci (peritumoral area) by the method of immuno???assay and using standard test systems. The following growth factor were detected: VEGF-A and its receptors VEGF-R1 (BenderMedSystem, Austria), VEGF-C and its receptor VEGF-R3 (BenderMedSystem, Austria), EGF (Biosource, USA), IFR-1 and IFR-2 (Mediagnost, USA), TGF-β1 (BenderMedSystem, Austria). Results. We have found both common and distinctive features in the content of growth factors in neoplastic tissues of different histological structure and corresponding peritumoral areas. Common metabolic features of glioblastomas, brain metastases and meningiomas include various increase in the level of VEGF-A, VEGF-R1, VEGF-C, IFR-1, IFR-2 and VEGF-C/VEGF-R3 index ratio. Differences included the fact that the level of VEGF-R3 and TGF-β1 did not increase in the benign tumor, while the level of EGF and VEGF-A/VEGF-R1 index ratio were below the control values in contrast to the values of malignant tumors. Conclusions • In the neoplastic tissues of glioblastomas and peritumoral area there is a strong positive correlation between the level of VEGF-A with the level of EGF, IGF-1, IGF-II and TGF-β1. • In the metastatic tissue there is a strong positive correlation between the level of VEGF-A with the level of EGF, IGF-1, IGF-II and TGF-β1. However, correlations had a different nature in the peritumoral zone tissues near to metastases: there was a strong positive correla???tion of VEGF-A level with TGF-β1 only, while there was a strong negative correlation with the level of IGF-1 and IGF-II, there were no correlations with EGF level. • In meningioma tissues VEGF-A levels correlated only with the level of insulin-like growth factors: there was a strong positive correlation with IGF-1 and IGF-II, correlation has been found with the level of EGF and TGF-β1. • In descending order VEGF-C was detected in glioblastoma tissue, in metastatic tumors, meningiomas, peritumoral zones of glioblastomas and metastases. However, in all of these samples the level of the studied factor significantly exceeded the value in intact brain tissue. VEGFR-3 level was elevated in glioblastoma tissue only.