Tumor dormancy in bone

Abstract

Background Bone marrow is a common site of metastasis for a number of tumor types, including breast, prostate, and lung cancer, but the mechanisms controlling tumor dormancy in bone are poorly understood. In breast cancer, while advances in drug development, screening practices, and surgical techniques have dramatically improved survival rates in recent decades, metastatic recurrence in the bone remains common and can develop years or decades after elimination of the primary tumor. Recent Findings It is now understood that tumor cells disseminate to distant metastatic sites at early stages of tumor progression, leaving cancer survivors at a high risk of recurrence. This review will discuss mechanisms of bone lesion development and current theories of how dormant cancer cells behave in bone, as well as a number of processes suspected to be involved in the maintenance of and exit from dormancy in the bone microenvironment. Conclusions The bone is a complex microenvironment with a multitude of cell types and processes. Many of these factors, including angiogenesis, immune surveillance, and hypoxia, are thought to regulate tumor cell entry and exit from dormancy in different bone marrow niches.

Cancer Treatment–Induced Bone Loss (CTIBL): State of the Art and Proper Management in Breast Cancer Patients on Endocrine Therapy

“…The most intriguing one regards the presence of bone undetectable micro-metastases established by circulating tumour cells that colonize the osteoblastic niche [84]. These BC micro-metastases can remain quiescent potentially for many years, until, for reasons that are not well understood, they exit their dormancy status and start to proliferate, thus generating macro-metastases in the bone or elsewhere [85]. Being bisphosphonates as well as denosumab active on bone cells and T cell function, they could counteract this event by inducing bone microenvironment modifications that may be lethal for isolated cancer cells [86].…”

Stromal Co-Cultivation for Modeling Breast Cancer Dormancy in the Bone Marrow

“…A number of three-dimensional (3D) and organotypic in vitro models have been developed to study cancer cell dormancy with variable components [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. Three-dimensional bone-mimicking scaffolds recapitulate rigidity and structural nuances [ 22 , 23 , 24 , 25 , 26 , 27 ].…”

“…Other models, including 3D models, mathematical models, biomaterials, microfluidics and bioreactors, have been developed. These are reviewed expertly elsewhere [ 15 , 17 , 20 , 21 , 28 ] and will not be discussed here. Much of what has been learned from tumor–stromal interactions was derived from 3D models, and those mechanisms will be cited here.…”

Mechanisms, Diagnosis and Treatment of Bone Metastases

“…Of note, the precise location and composition of the bone “metastatic niche” of different cancers are poorly defined. It has been proposed to comprise a hematopoietic stem cell (HSC), endosteal (osteoclasts, osteoblasts, osteocytes, fibroblasts) and vascular (endothelial cells, pericytes) niche compartment [ 13 , 77 , 78 ]. A role in breast cancer colonization of the bone has also been assigned to the adipose tissue compartment in the bone marrow [ 79 ].…”

“…Solitary disseminated primary tumor cells, once settled in the bone niche, may grow immediately or adopt a nonproliferating dormant state remaining quiescent in the bone marrow for up to decades (“cellular dormancy”) [ 78 , 86 , 87 ]. A comprehensive mechanistic insight into tumor dormancy, including its implications in tumor invasion and metastasis, has recently been provided [ 88 ].…”