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      Bone Microenvironment and Osteosarcoma Metastasis

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          Abstract

          The bone microenvironment is an ideal fertile soil for both primary and secondary tumors to seed. The occurrence and development of osteosarcoma, as a primary bone tumor, is closely related to the bone microenvironment. Especially, the metastasis of osteosarcoma is the remaining challenge of therapy and poor prognosis. Increasing evidence focuses on the relationship between the bone microenvironment and osteosarcoma metastasis. Many elements exist in the bone microenvironment, such as acids, hypoxia, and chemokines, which have been verified to affect the progression and malignance of osteosarcoma through various signaling pathways. We thoroughly summarized all these regulators in the bone microenvironment and the transmission cascades, accordingly, attempting to furnish hints for inhibiting osteosarcoma metastasis via the amelioration of the bone microenvironment. In addition, analysis of the cross-talk between the bone microenvironment and osteosarcoma will help us to deeply understand the development of osteosarcoma. The cellular and molecular protagonists presented in the bone microenvironment promoting osteosarcoma metastasis will accelerate the exploration of novel therapeutic strategies towards osteosarcoma.

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          Most cited references116

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          Tumour formation involves the co-evolution of neoplastic cells together with extracellular matrix, tumour vasculature and immune cells. Successful outgrowth of tumours and eventual metastasis is not determined solely by genetic alterations in tumour cells, but also by the fitness advantage such mutations confer in a given environment. As fitness is context dependent, evaluating tumours as complete organs, and not simply as masses of transformed epithelial cells, becomes paramount. The dynamic tumour topography varies drastically even throughout the same lesion. Heterologous cell types within tumours can actively influence therapeutic response and shape resistance.
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            Wnt/beta-catenin signaling in development and disease.

            A remarkable interdisciplinary effort has unraveled the WNT (Wingless and INT-1) signal transduction cascade over the last two decades. Wnt genes encode small secreted proteins that are found in all animal genomes. Wnt signaling is involved in virtually every aspect of embryonic development and also controls homeostatic self-renewal in a number of adult tissues. Germline mutations in the Wnt pathway cause several hereditary diseases, and somatic mutations are associated with cancer of the intestine and a variety of other tissues.
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              Tumor microenvironment complexity and therapeutic implications at a glance

              The dynamic interactions of cancer cells with their microenvironment consisting of stromal cells (cellular part) and extracellular matrix (ECM) components (non-cellular) is essential to stimulate the heterogeneity of cancer cell, clonal evolution and to increase the multidrug resistance ending in cancer cell progression and metastasis. The reciprocal cell-cell/ECM interaction and tumor cell hijacking of non-malignant cells force stromal cells to lose their function and acquire new phenotypes that promote development and invasion of tumor cells. Understanding the underlying cellular and molecular mechanisms governing these interactions can be used as a novel strategy to indirectly disrupt cancer cell interplay and contribute to the development of efficient and safe therapeutic strategies to fight cancer. Furthermore, the tumor-derived circulating materials can also be used as cancer diagnostic tools to precisely predict and monitor the outcome of therapy. This review evaluates such potentials in various advanced cancer models, with a focus on 3D systems as well as lab-on-chip devices. Video abstract
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                23 September 2020
                October 2020
                : 21
                : 19
                : 6985
                Affiliations
                [1 ]Lab for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, China; yangchaofei@ 123456mail.nwpu.edu.cn (C.Y.); tianye@ 123456nwpu.edu.cn (Y.T.); sofan@ 123456mail.nwpu.edu.cn (F.Z.); chzhh@ 123456mail.nwpu.edu.cn (Z.C.); suph@ 123456mail.nwpu.edu.cn (P.S.); liyu@ 123456nwpu.edu.cn (Y.L.)
                [2 ]Research Center for Special Medicine and Health Systems Engineering, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, China
                [3 ]NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, China
                Author notes
                [* ]Correspondence: qianair@ 123456nwpu.edu.cn ; Tel.: +86-29-8849-1840
                [†]

                These authors contribute equally to this work.

                Author information
                https://orcid.org/0000-0001-7053-5447
                https://orcid.org/0000-0001-5317-6374
                https://orcid.org/0000-0002-1462-0783
                https://orcid.org/0000-0002-0740-9218
                Article
                ijms-21-06985
                10.3390/ijms21196985
                7582690
                32977425
                9d4dec89-6820-42db-af43-1143a9844bba
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 18 August 2020
                : 22 September 2020
                Categories
                Review

                Molecular biology
                bone microenvironment,metastasis,osteosarcoma,primary bone tumor,signal pathway
                Molecular biology
                bone microenvironment, metastasis, osteosarcoma, primary bone tumor, signal pathway

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