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

Center for Research and Medical Studies (CeRMS), A.O.U. Città della Salute e della Scienza, 10126 Turin, Italy
Department of Surgical Sciences (DISC), Orthopaedic Clinic-IRCCS A.O.U. San Martino, 16132 Genoa, Italy
Author to whom correspondence should be addressed.
Cancers 2018, 10(2), 56;
Received: 5 December 2017 / Revised: 12 February 2018 / Accepted: 17 February 2018 / Published: 20 February 2018
(This article belongs to the Special Issue Targeting Bone Metastasis in Cancer)
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. View Full-Text
Keywords: bone metastases; cancer stem cells; osteotropism bone metastases; cancer stem cells; osteotropism
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MDPI and ACS Style

Roato, I.; Ferracini, R. Cancer Stem Cells, Bone and Tumor Microenvironment: Key Players in Bone Metastases. Cancers 2018, 10, 56.

AMA Style

Roato I, Ferracini R. Cancer Stem Cells, Bone and Tumor Microenvironment: Key Players in Bone Metastases. Cancers. 2018; 10(2):56.

Chicago/Turabian Style

Roato, Ilaria; Ferracini, Riccardo. 2018. "Cancer Stem Cells, Bone and Tumor Microenvironment: Key Players in Bone Metastases" Cancers 10, no. 2: 56.

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