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      Understanding the Progression of Bone Metastases to Identify Novel Therapeutic Targets

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          Abstract

          Bone is one of the most preferential target site for cancer metastases, particularly for prostate, breast, kidney, lung and thyroid primary tumours. Indeed, numerous chemical signals and growth factors produced by the bone microenvironment constitute factors promoting cancer cell invasion and aggression. After reviewing the different theories proposed to provide mechanism for metastatic progression, we report on the gene expression profile of bone-seeking cancer cells. We also discuss the cross-talk between the bone microenvironment and invading cells, which impacts on the tumour actions on surrounding bone tissue. Lastly, we detail therapies for bone metastases. Due to poor prognosis for patients, the strategies mainly aim at reducing the impact of skeletal-related events on patients’ quality of life. However, recent advances have led to a better understanding of molecular mechanisms underlying bone metastases progression, and therefore of novel therapeutic targets.

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          Most cited references110

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          The distribution of secondary growths in cancer of the breast. 1889.

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            The metastatic niche: adapting the foreign soil.

            The 'seed and soil' hypothesis for metastasis sets forth the concept that a conducive microenvironment, or niche, is required for disseminating tumour cells to engraft distant sites. This Opinion presents emerging data that support this concept and outlines the potential mechanism and temporal sequence by which changes occur in tissues distant from the primary tumour. To enable improvements in the prognosis of advanced malignancy, early interventions that target both the disseminating seed and the metastatic soil are likely to be required.
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              Molecular basis of metastasis.

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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
                04 January 2018
                January 2018
                : 19
                : 1
                : 148
                Affiliations
                [1 ]Centre National de la Recherche Scientifique (CNRS), Université Côte d’Azur, Inserm, iBV, 06108 Nice, France; Annie.SCHMID-ALLIANA@ 123456unice.fr (A.S.-A.); Heidy.SCHMID-ANTOMARCHI@ 123456unice.fr (H.S.-A.); rasha.al-sahlanee@ 123456unice.fr (R.A.-S.); Patricia.Lagadec@ 123456unice.fr (P.L.); jean-claude.scimeca@ 123456unice.fr (J.-C.S.)
                [2 ]College of Sciences, Biotechnology Department, University of Bagdad, Bagdad, Iraq
                [3 ]Regenerative Medicine and Skeleton. RMeS-Lab, INSERM UMR 1229, University of Nantes, 44000 Nantes, France
                [4 ]Chimie et Interdisciplinarité, Synthèse, Analyse, Modélisation (CEISAM), UMR CNRS 6230, University of Nantes, 44300 Nantes, France
                [5 ]Faculty of Pharmaceutical Sciences, University of Nantes, 44000 Nantes, France
                Author notes
                [* ]Correspondence: elise.verron@ 123456univ-nantes.fr ; Tel.: +33-2-53-48-43-05
                [†]

                Contributed equally to this manuscript.

                Article
                ijms-19-00148
                10.3390/ijms19010148
                5796097
                29300334
                0f193a39-5c63-440a-8819-630b75d136cf
                © 2018 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
                : 21 November 2017
                : 02 January 2018
                Categories
                Review

                Molecular biology
                bone metastases,bone tropism,bone microenvironment,molecular mechanisms,therapeutic strategies

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