Bone as a Preferential Site for Metastasis

Abstract

Bone marrow provides a unique microenvironment favoring the colonization and outgrowth of metastatic tumor cells. Despite the high incidence of bone metastasis in breast and prostate cancer patients, many of the molecular mechanisms controlling metastatic progression remain unclear. Several gene signatures associated with bone metastasis have been reported, but no metastasis‐specific gene alterations have been identified. Therefore, there has been considerable interest in understanding how the bone microenvironment impacts the behavior of disseminated tumor cells (DTCs) prior to and following colonization of the bone. Substantial evidence indicates that disruption of normal bone homeostasis by tumor‐derived factors establishes a premetastatic niche within the bone that favors DTC colonization. Following dissemination, bone resident cells and the surrounding stroma provide critical signals that support tumor cell colonization, survival, and eventual outgrowth. Clinical data suggest that patients can harbor DTCs for years to decades prior to developing overt bone metastases, suggesting a period of tumor dormancy occurs in the bone marrow. Several dormancy‐promoting factors have been recently identified; however, critical questions surrounding the molecular triggers and timing of tumor cell emergence from dormancy remain. Here, we review how metastatic tumor cells co‐opt the bone marrow microenvironment for metastatic progression and discuss emerging insights into how to more effectively target DTCs and prevent metastasis. © 2018 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research

A Potential Role of RUNX2- RUNT Domain in Modulating the Expression of Genes Involved in Bone Metastases: An In Vitro Study with Melanoma Cells

“…The bone microenvironment regulates complex and relevant processes such as hematopoiesis, osteogenesis and osteolysis [1]. Various studies demonstrated that different molecular mechanisms are involved in promoting cancer cells residency in bone through chemotaxis in bone niches [25]. Most bone metastases occur when prostate, breast and lung primary tumors spread to the bone [26,27].…”

Site‐specific metastasis: A cooperation between cancer cells and the metastatic microenvironment

“…Dormancy induction of bone‐metastasizing prostate cancer cells represents a typical case of MME‐regulated dormancy at a specific organ site. TGFβ2, 181 bone morphogenetic proteins (BMP) 182 and other factors 183 induce dormancy of prostate cancer cells in the bone. The mechanism underlying this site‐specific dormancy is an alteration in the ERK and p38 MAPK signaling ratio so as to create a high p38 and a low ERK signaling 184 .…”

Innovative Options for Bone Metastasis Treatment: An Extensive Analysis on Biomaterials-Based Strategies for Orthopedic Surgeons

“…produced by osteoblasts, stored in bone matrix, and released during physiological bone disruption becoming bioavailable for cancer cells ( Florencio-Silva et al, 2015 ; Owen and Parker, 2019 ). In addition, the primary tumor sends systemic signals to set and prepare suitable soil for the metastasis, the so called premetastatic niche (PMN), where stromal cells are also recruited to host cancer cells ( Owen and Parker, 2019 ; Sowder and Johnson, 2019 ).…”