A Correlation Between Intracellular Zinc Content and Osteosarcoma
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A Correlation Between Intracellular Zinc Content and Osteosarcoma Azadeh Meshkini 1 Received: 22 August 2020 / Accepted: 28 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Zinc is a trace element in human body involved in many biological processes. It is critical for cell growth and acts as a cofactor for the structure and function of a wide range of cellular proteins such as enzymes. Mounting evidence has shown the involvement of intracellular zinc in the bone-related biological processes such as bone growth, homeostasis, and regeneration; however, the molecular mechanism(s) whereby zinc impels tumorigenesis in bone remains largely unexplored. In this article, selective outline related to the content of intracellular zinc in osteosarcoma cells was provided, and its correlation with signaling molecules that are activated and consequently guide the cells toward tumorigenesis or osteogenesis was discussed. Based on preclinical and clinical evidence, dysregulation of zinc homeostasis, both at intracellular and tissue level, has the main role in the pathogenesis of osteosarcoma. Based on the intracellular zinc content, this element could have a direct role in the dynamics of bone cell transformation and tumor development and play an indirect role in the modulation of the inflammatory and pro/ antitumorigenic responses in immune cells. In this context, zinc transporters and the proteins containing zinc domain are regulated by the availability of zinc, playing a crucial role in bone cell transformation and differentiation. According to recent studies, it seems that intracellular zinc levels could be considered as an early prognosis marker. Besides, identification and targeting of zinc-dependent signaling molecules could tilt the balance of life and death toward the latter in chemoresistant malignant cells and may pave a way for designing of the novel osteosarcoma treatment strategies. Keywords Zinc . Bone . Osteosarcoma . Chemoresistance
Introduction Osteosarcoma is the most prevalent malignant primary bone tumor in children and adolescents and the second leading cause of mortality in this age group. Tumor cells penetrate to and destroy the cortex of the bone and then extend to the surrounding soft tissue. Osteosarcoma is highly aggressive with a high propensity for pulmonary metastasis, and 90% of patients die even after radical surgeries such as amputation [1]. It has been reported that the etiology of osteosarcoma is associated with germline mutations in suppressor genes, indicating a correlation between these genes and the occurrence of the disease [2]. The standard chemotherapeutic modality consists of the administration of a combination of chemotherapeutic drugs such as doxorubicin, cisplatin, and methotrexate that is followed by surgery and adjuvant chemotherapy with the same agents. However, regarding further attempts to raise * Azadeh Meshkini [email protected] 1
Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad P. O. Box 91779489
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