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Cancer Stem Cells, Bone and Tumor Microenvironment: Key Players in Bone Metastases

Tumor mass is constituted by a heterogeneous group of cells, among which a key role is played by the cancer stem cells (CSCs), possessing high regenerative properties. CSCs directly metastasize to bone, since bone microenvironment represents a fertile environment that protects CSCs against the immun...

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Detalles Bibliográficos
Autores principales: Roato, Ilaria, Ferracini, Riccardo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836088/
https://www.ncbi.nlm.nih.gov/pubmed/29461491
http://dx.doi.org/10.3390/cancers10020056
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author Roato, Ilaria
Ferracini, Riccardo
author_facet Roato, Ilaria
Ferracini, Riccardo
author_sort Roato, Ilaria
collection PubMed
description Tumor mass is constituted by a heterogeneous group of cells, among which a key role is played by the cancer stem cells (CSCs), possessing high regenerative properties. CSCs directly metastasize to bone, since bone microenvironment represents a fertile environment that protects CSCs against the immune system, and maintains their properties and plasticity. CSCs can migrate from the primary tumor to the bone marrow (BM), due to their capacity to perform the epithelial-to-mesenchymal transition. Once in BM, they can also perform the mesenchymal-to-epithelial transition, allowing them to proliferate and initiate bone lesions. Another factor explaining the osteotropism of CSCs is their ability to recognize chemokine gradients toward BM, through the CXCL12–CXCR4 axis, also known to be involved in tumor metastasis to other organs. Moreover, the expression of CXCR4 is associated with the maintenance of CSCs’ stemness, and CXCL12 expression by osteoblasts attracts CSCs to the BM niches. CSCs localize in the pre-metastatic niches, which are anatomically distinct regions within the tumor microenvironment and govern the metastatic progression. According to the stimuli received in the niches, CSCs can remain dormant for long time or outgrow from dormancy and create bone lesions. This review resumes different aspects of the CSCs’ bone metastastic process and discusses available treatments to target CSCs.
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spelling pubmed-58360882018-03-07 Cancer Stem Cells, Bone and Tumor Microenvironment: Key Players in Bone Metastases Roato, Ilaria Ferracini, Riccardo Cancers (Basel) Review Tumor mass is constituted by a heterogeneous group of cells, among which a key role is played by the cancer stem cells (CSCs), possessing high regenerative properties. CSCs directly metastasize to bone, since bone microenvironment represents a fertile environment that protects CSCs against the immune system, and maintains their properties and plasticity. CSCs can migrate from the primary tumor to the bone marrow (BM), due to their capacity to perform the epithelial-to-mesenchymal transition. Once in BM, they can also perform the mesenchymal-to-epithelial transition, allowing them to proliferate and initiate bone lesions. Another factor explaining the osteotropism of CSCs is their ability to recognize chemokine gradients toward BM, through the CXCL12–CXCR4 axis, also known to be involved in tumor metastasis to other organs. Moreover, the expression of CXCR4 is associated with the maintenance of CSCs’ stemness, and CXCL12 expression by osteoblasts attracts CSCs to the BM niches. CSCs localize in the pre-metastatic niches, which are anatomically distinct regions within the tumor microenvironment and govern the metastatic progression. According to the stimuli received in the niches, CSCs can remain dormant for long time or outgrow from dormancy and create bone lesions. This review resumes different aspects of the CSCs’ bone metastastic process and discusses available treatments to target CSCs. MDPI 2018-02-20 /pmc/articles/PMC5836088/ /pubmed/29461491 http://dx.doi.org/10.3390/cancers10020056 Text en © 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/).
spellingShingle Review
Roato, Ilaria
Ferracini, Riccardo
Cancer Stem Cells, Bone and Tumor Microenvironment: Key Players in Bone Metastases
title Cancer Stem Cells, Bone and Tumor Microenvironment: Key Players in Bone Metastases
title_full Cancer Stem Cells, Bone and Tumor Microenvironment: Key Players in Bone Metastases
title_fullStr Cancer Stem Cells, Bone and Tumor Microenvironment: Key Players in Bone Metastases
title_full_unstemmed Cancer Stem Cells, Bone and Tumor Microenvironment: Key Players in Bone Metastases
title_short Cancer Stem Cells, Bone and Tumor Microenvironment: Key Players in Bone Metastases
title_sort cancer stem cells, bone and tumor microenvironment: key players in bone metastases
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836088/
https://www.ncbi.nlm.nih.gov/pubmed/29461491
http://dx.doi.org/10.3390/cancers10020056
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