Lu Yao1, Yong Wang2, Wei Ma3, Xuezhe Han3, Xijing He4, Xing Dai5. 1. Department of Orthopaedics, The First Affiliated Hospital, Health Science Center, Xi'an Jiaotong University, Xi'an, China; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an, China. 2. Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an, China. 3. Department of Orthopaedics, The First Affiliated Hospital, Health Science Center, Xi'an Jiaotong University, Xi'an, China. 4. Department of Orthopaedics, The Second Affiliated Hospital, Health Science Center, Xi'an Jiaotong University, Xi'an, China. 5. Department of Orthopaedics, The First Affiliated Hospital, Health Science Center, Xi'an Jiaotong University, Xi'an, China. Electronic address: goldendai@xjtu.edu.cn.
Abstract
BACKGROUND AND AIMS: Osteosarcoma is one of the most pernicious primary bone tumor characterized by high malignancy and metastasis, however its pathogenesis remain largely unknown. Our previous study showed elevated expression of adrenomedullin (ADM) is correlated with prognosis and disease severity in osteosarcoma patients. In this research, we continue to study the mechanisms of ADM-induced osteosarcoma cells proliferation in vitro and in vivo osteosarcoma models. METHODS: The Radioimmunoassay was used to test the correlations of ADM and vascular endothelial growth factor (VEGF) expressions in plasma of osteosarcoma patients. The MTT and flow cytometry analysis were accepted to monitor the proliferation of osteosarcoma cells, meanwhile the ADM and VEGF expression were detected by real-time PCR and western blot. Moreover, the relationship among ADM and VEGF expression was also assessed in the osteosarcoma nude mice models. RESULTS: In this study, a significant correlation was found between ADM and VEGF expression in the plasma of osteosarcoma patients. As important stimuli in osteosarcoma proliferation, hypoxia could stimulate ADM and VEGF expression in MG-63 cells. The expressions of ADM and VEGF increased with the duration of hypoxia, which also identify the positive correlations between the expression of ADM and VEGF. The proliferation of MG-63 cells decreased when ADM was inhibited. And the proliferation increased when adding exogenous ADM, while VEGF inhibition attenuated this effect. Furthermore, ADM reduction also inhibited VEGF, CD31 expression and tumor cells growth in osteosarcoma nude mice models. CONCLUSION: These results suggested inhibition of osteosarcoma cells proliferation might be influenced by ADM through VEGF pathway, which implied ADM-VEGF signal was a potential target for impeding the proliferation of malignant cells in osteosarcoma.
BACKGROUND AND AIMS: Osteosarcoma is one of the most pernicious primary bone tumor characterized by high malignancy and metastasis, however its pathogenesis remain largely unknown. Our previous study showed elevated expression of adrenomedullin (ADM) is correlated with prognosis and disease severity in osteosarcomapatients. In this research, we continue to study the mechanisms of ADM-induced osteosarcoma cells proliferation in vitro and in vivo osteosarcoma models. METHODS: The Radioimmunoassay was used to test the correlations of ADM and vascular endothelial growth factor (VEGF) expressions in plasma of osteosarcomapatients. The MTT and flow cytometry analysis were accepted to monitor the proliferation of osteosarcoma cells, meanwhile the ADM and VEGF expression were detected by real-time PCR and western blot. Moreover, the relationship among ADM and VEGF expression was also assessed in the osteosarcomanude mice models. RESULTS: In this study, a significant correlation was found between ADM and VEGF expression in the plasma of osteosarcomapatients. As important stimuli in osteosarcoma proliferation, hypoxia could stimulate ADM and VEGF expression in MG-63 cells. The expressions of ADM and VEGF increased with the duration of hypoxia, which also identify the positive correlations between the expression of ADM and VEGF. The proliferation of MG-63 cells decreased when ADM was inhibited. And the proliferation increased when adding exogenous ADM, while VEGF inhibition attenuated this effect. Furthermore, ADM reduction also inhibited VEGF, CD31 expression and tumor cells growth in osteosarcomanude mice models. CONCLUSION: These results suggested inhibition of osteosarcoma cells proliferation might be influenced by ADM through VEGF pathway, which implied ADM-VEGF signal was a potential target for impeding the proliferation of malignant cells in osteosarcoma.
Authors: A Losada-García; S A Cortés-Ramírez; M Cruz-Burgos; M Morales-Pacheco; Carlos D Cruz-Hernández; Vanessa Gonzalez-Covarrubias; Carlos Perez-Plascencia; M A Cerbón; M Rodríguez-Dorantes Journal: Front Genet Date: 2022-01-17 Impact factor: 4.599