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Maurizi et al. J Cancer Metastasis Treat 2021;7:35 Journal of Cancer
DOI: 10.20517/2394-4722.2021.74
Metastasis and Treatment

Review Open Access

How the “seed” prepares the “soil”: the bone/bone
marrow pre-metastatic niche

Antonio Maurizi, Marco Ponzetti, Nadia Rucci

Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila 67100, Italy.
Correspondence to: Dr. Nadia Rucci, Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, Via
Vetoio-Coppito 2, L’Aquila 67100, Italy. E-mail: rucci@univaq.it

How to cite this article: Maurizi A, Ponzetti M, Rucci N. How the “seed” prepares the “soil”: the bone/bone marrow pre-
metastatic niche. J Cancer Metastasis Treat 2021;7:35. https://dx.doi.org/10.20517/2394-4722.2021.74

Received: 29 May 2021 First Decision: 28 Apr 2021 Revised: 30 Apr 2021 Accepted: 28 May 2021 First online: 8 Jun 2021

Academic Editor: Lucio Miele Copy Editor: Yue-Yue Zhang Production Editor: Yue-Yue Zhang

Abstract
Cancer is one of the leading causes of death in women and men worldwide. The fatal outcome usually occurs after
metastatic dissemination, and bone is by far the most common site of metastasis for breast and prostate cancer,
the highest incidence neoplasia in women and men, respectively. However, while this is clear, the mechanisms
through which the metastatic preference is established is not. An emerging concept in this regard is the pre-
metastatic niche (PMN) establishment, i.e., the process through which tumors can influence the bone
microenvironment from the primary site and make it permissive for their engraftment, before they migrate to the
blood flow and metastasize. In this review, we discuss key microenvironmental players in the bone/bone marrow
PMN, including osteoblasts, osteoclasts, and bone marrow adipocytes. We also describe the known PMN-
educating factors, as well as the role of extracellular vesicles as emerging players in the bone/bone marrow PMN.
An overview of current therapeutic developments aimed at targeting the bone PMN is also provided.

Keywords: Bone metastasis, pre-metastatic niche, bone microenvironment, extracellular vesicles

INTRODUCTION
Cancer is one of the most common classes of non-transmittable diseases and one of the leading causes of
death in women and men worldwide . The fatal outcome usually occurs after metastatic dissemination of
[1]
cancer cells from the primary tumor. In fact, even though considerable effort has been put into cancer

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0
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