Angiogenic systemic response to the hypoxic microenvironment in prostate tumorigenesis: A pilot study.

Abstract

The present paper aimed to investigate the altered angiogenetic mechanisms in hypoxic conditions in patients with prostate tumours, in correlation with common clinicopathologic variables. A case-control study was developed and included 87 patients with prostate tumours [40 diagnosed with benign prostatic hyperplasia (BPH) and 47 diagnosed with prostate cancer (PCa), using prostate transrectal biopsy] and 40 healthy subjects. The following parameters were evaluated in the serum of volunteers: Hypoxia-inducible factor (HIF)-1α, fibroblast growth factor (FGF)-2, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2 and -9, thrombospondin (TSP)-1 and soluble VEGF-1 receptor. Experimental data analysis demonstrated increasing amounts of inflammation in patients with PCa (IL-6, 18.1±4.7 ng/ml) and BPH (IL-6, 16.3±5.1 ng/ml) vs. control (IL-6, 4.1±1.2 ng/ml); overregulation of HIF1α in patients with PCa (129.3±21.8 ng/ml) compared with patients with BPH (65.6±18.2 ng/ml) and control (61.3±12.7 ng/ml); angiogenesis abnormalities in patients with PCa (upregulation of FGF-2, VEGF, MMP-2 and -9, suppression of TSP-1 and soluble VEGR-1) and BPH (upregulation FGF-2 and VEGF) compared with the control group. In conclusion, a greater understanding of the biological mechanism, the pathological roles and the clinical significance of various proangiogenic parameters and angiogenic-suppressor proteins seem useful in clinical practice for establishing an early diagnosis of prostate pathology and finding an individualized therapeutic approach.