Exploiting bone niches: progression of disseminated tumor cells to metastasis

Abstract

niches may dictate the cellular fates and therapeutic responses of DTCs and microscopic metastases. Cancer cells may exploit the niches' normal roles, including protection from aberrant immune activation and remodeling/repair of bones, to facilitate metastatic progression. Therefore, identification of the cancer-niche crosstalk pathways, especially those involved in immunosurveillance and tissue repair, may lead to novel mechanistic insights and therapeutic targets.There are challenges and opportunities in our further investigations of BM niches in metastatic colonization. Bone-resident cells apparently of the same type may actually be heterogeneous with regard to the location, lineage, and functions. This is exemplified by pericytes/MSCs (195,196) and endothelial cells (197), which may reconcile the seemingly contradictory findings (e.g., refs. 81, 87). Future studies are needed for more precise definition of various niches. To this end, single-cell transcriptomic or proteomic analyses that preserve the spatial information may be highly valu-

Spontaneous Osteoclastogenesis, a risk factor for bone metastasis in advanced luminal A-type breast cancer patients

“…We have previously shown higher levels of RANKL in PB plasma from untreated advanced BCPs (stage III); thus PB-OCPs (RANK+) could be responsible in part for the observed peripheral SpOC (37). In BM derived cells from BCPs, CD14 and CD11b markers are higher expressed than in HVs evidencing not only an activation of OCPs but also suggesting the putative identification of myeloid derived suppressor cells (6,51). Further evidence in this direction has to be BCPs (n=10) vs HVs (n=14)…”

“…We have previously shown higher levels of RANKL in PB plasma from untreated advanced BCPs (stage III); thus PB-OCPs (RANK+) could be responsible in part for the observed peripheral SpOC ( 37 ). In BM derived cells from BCPs, CD14 and CD11b markers are higher expressed than in HVs evidencing not only an activation of OCPs but also suggesting the putative identification of myeloid derived suppressor cells ( 6 , 51 ). Further evidence in this direction has to be collected, however, the possibility of promoting a hospitable bone microenvironment for tumor cells both by shutting anti-tumor immune response and releasing growth factors via bone resorption would denote a key finding in the maintenance of the “vicious cycle”.…”

Research progress of bone metastases: From disease recognition to clinical practice

“…These related cytokines may play a key role in circulating tumor cell dormancy in bone metastases or in tumor cell proliferation in metastatic sites. CD8+T cells are also regulated by immature myeloid cells and osteoblasts ( 94 ). In non-specific immunity, macrophages, especially tumor-associated macrophages(TAMs), have a great influence on the pathogenesis of metastatic tumors ( 95 ).…”

Perspective Chapter: Breast-Tumor-Derived Bone Pre-Metastatic Disease – Interplay between Immune and Bone Cells within Bone Marrow Microenvironment

“…Interestingly, patients without any metastases harbored disseminated breast cancer cells with less genetic heterogeneity compared with the primary tumor or those disseminated cells isolated from bone metastatic patients [175,178]. Of note, less than 0.1% of disseminated breast cancer cells survive during circulation and homing [179][180][181]. Based on these Breast-Tumor-Derived Bone Pre-Metastatic Disease: Interplay between Immune and Bone Cells… DOI: http://dx.doi.org/10.5772/intechopen.107278 findings, we can speculate that bone/BM stromal cellular and molecular components probably play roles in supporting these mutations, for further licensing and selection of the best "seeds" to adapt in the pre-metastatic niche, until their overt bone colonization.…”