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      Extracellular BMP Antagonists, Multifaceted Orchestrators in the Tumor and Its Microenvironment

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          Abstract

          The bone morphogenetic proteins (BMPs), a subgroup of the transforming growth factor-β (TGF-β) superfamily, are involved in multiple biological processes such as embryonic development and maintenance of adult tissue homeostasis. The importance of a functional BMP pathway is underlined by various diseases, including cancer, which can arise as a consequence of dysregulated BMP signaling. Mutations in crucial elements of this signaling pathway, such as receptors, have been reported to disrupt BMP signaling. Next to that, aberrant expression of BMP antagonists could also contribute to abrogated signaling. In this review we set out to highlight how BMP antagonists affect not only the cancer cells, but also the other cells present in the microenvironment to influence cancer progression.

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          Most cited references74

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          A framework for advancing our understanding of cancer-associated fibroblasts

          Cancer-associated fibroblasts (CAFs) are a key component of the tumour microenvironment with diverse functions, including matrix deposition and remodelling, extensive reciprocal signalling interactions with cancer cells and crosstalk with infiltrating leukocytes. As such, they are a potential target for optimizing therapeutic strategies against cancer. However, many challenges are present in ongoing attempts to modulate CAFs for therapeutic benefit. These include limitations in our understanding of the origin of CAFs and heterogeneity in CAF function, with it being desirable to retain some antitumorigenic functions. On the basis of a meeting of experts in the field of CAF biology, we summarize in this Consensus Statement our current knowledge and present a framework for advancing our understanding of this critical cell type within the tumour microenvironment.
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            Microenvironmental regulation of metastasis.

            Metastasis is a multistage process that requires cancer cells to escape from the primary tumour, survive in the circulation, seed at distant sites and grow. Each of these processes involves rate-limiting steps that are influenced by non-malignant cells of the tumour microenvironment. Many of these cells are derived from the bone marrow, particularly the myeloid lineage, and are recruited by cancer cells to enhance their survival, growth, invasion and dissemination. This Review describes experimental data demonstrating the role of the microenvironment in metastasis, identifies areas for future research and suggests possible new therapeutic avenues.
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              Why don't we get more cancer? A proposed role of the microenvironment in restraining cancer progression.

              Tumors are like new organs and are made of multiple cell types and components. The tumor competes with the normal microenvironment to overcome antitumorigenic pressures. Before that battle is won, the tumor may exist within the organ unnoticed by the host, referred to as 'occult cancer'. We review how normal tissue homeostasis and architecture inhibit progression of cancer and how changes in the microenvironment can shift the balance of these signals to the procancerous state. We also include a discussion of how this information is being tailored for clinical use.
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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
                29 May 2020
                June 2020
                : 21
                : 11
                : 3888
                Affiliations
                Department of Gastroenterology and Hepatology, Leiden University Medical Centre, 2333 ZA Leiden, The Netherlands; S.ouahoud@ 123456lumc.nl (S.O.); J.C.H.Hardwick@ 123456lumc.nl (J.C.H.H.)
                Author notes
                [* ]Correspondence: L.J.A.C.Hawinkels@ 123456lumc.nl ; Tel.:+31-71-526-6736
                Author information
                https://orcid.org/0000-0003-0547-1023
                https://orcid.org/0000-0002-9575-5099
                https://orcid.org/0000-0002-2274-9325
                Article
                ijms-21-03888
                10.3390/ijms21113888
                7313454
                32486027
                ad59c1bb-1d64-45e3-9906-9197a2bf05da
                © 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
                : 24 April 2020
                : 23 May 2020
                Categories
                Review

                Molecular biology
                bone morphogenetic proteins,antagonists,noggin,gremlin,tumor microenvironment,cancer
                Molecular biology
                bone morphogenetic proteins, antagonists, noggin, gremlin, tumor microenvironment, cancer

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