PURPOSE: Testicular cancer is the most frequent solid tumor in young male adults and a disease with elusive pathogenesis. The purpose of this study was to determine the role of matrix metalloproteinases and angiogenic factors in the pathogenesis of testicular germ cell tumors (GCTs). METHODS: Between 2003 and 2006 we measured the serum levels of matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), vascular endothelial growth factor A (VEGF-A), basic fibroblast growth factor (bFGF), platelet derived growth factor BB (PDGF-BB) and angiopoietin 2 (Ang-2) in 50 patients with testicular GCTs, at baseline, one month after the completion of the second cycle of chemotherapy and one year after the completion of chemotherapy, and in 16 male age-matched controls at baseline. RESULTS: At baseline, mean TIMP-2 value was lower in patients than controls, mean MMP-2/TIMP-2 ratio was higher in patients than controls and MMP9/TIMP-2 ratio was also higher. Ang-2 value was higher in patients than controls and bFGF value was also higher. Comparisons of the same parameters were also made among the 3 consecutive serum samples of the patients. All parameters normalized after chemotherapy except Ang-2 which remained elevated. CONCLUSION: The present study supports the hypothesis that tumor invasion and angiogenesis play a role in testicular GCTs pathogenesis. Also an interesting hypothesis was formed, concerning the role of elevated levels of Ang-2 found in testicular GCTs patients in the pathogenesis of the increased long term cardiovascular morbidity of these patients. Larger prospective studies are needed to confirm our results.
PURPOSE:Testicular cancer is the most frequent solid tumor in young male adults and a disease with elusive pathogenesis. The purpose of this study was to determine the role of matrix metalloproteinases and angiogenic factors in the pathogenesis of testicular germ cell tumors (GCTs). METHODS: Between 2003 and 2006 we measured the serum levels of matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), vascular endothelial growth factor A (VEGF-A), basic fibroblast growth factor (bFGF), platelet derived growth factor BB (PDGF-BB) and angiopoietin 2 (Ang-2) in 50 patients with testicular GCTs, at baseline, one month after the completion of the second cycle of chemotherapy and one year after the completion of chemotherapy, and in 16 male age-matched controls at baseline. RESULTS: At baseline, mean TIMP-2 value was lower in patients than controls, mean MMP-2/TIMP-2 ratio was higher in patients than controls and MMP9/TIMP-2 ratio was also higher. Ang-2 value was higher in patients than controls and bFGF value was also higher. Comparisons of the same parameters were also made among the 3 consecutive serum samples of the patients. All parameters normalized after chemotherapy except Ang-2 which remained elevated. CONCLUSION: The present study supports the hypothesis that tumor invasion and angiogenesis play a role in testicular GCTs pathogenesis. Also an interesting hypothesis was formed, concerning the role of elevated levels of Ang-2 found in testicular GCTs patients in the pathogenesis of the increased long term cardiovascular morbidity of these patients. Larger prospective studies are needed to confirm our results.
Authors: Michael A Paltsev; Victoria O Polyakova; Igor M Kvetnoy; George Anderson; Tatiana V Kvetnaia; Natalia S Linkova; Ekaterina M Paltseva; Rosa Rubino; Salvatore De Cosmo; Angelo De Cata; Gianluigi Mazzoccoli Journal: Oncotarget Date: 2016-03-15