Bone Metastasis niche in Breast Cancer


Bone metastasis is one of the most common complications of advanced breast cancer. During dissemination to bone, breast cancer cells locate in a putative ‘metastatic niche’, a microenvironment that regulates the colonisation, maintenance of tumour cell dormancy and subsequent tumour growth. The precise location and composition of the bone metastatic niche is not clearly defined. We have used in vivo models of early breast cancer dissemination to provide novel evidence that demonstrates overlap between endosteal, perivascular, HSC and the metastatic niche in bone.

Metastatic breast cancer remains a major cause of female cancer-related deaths, despite the improvements in early detection and therapy introduced over the past decades. The most frequent metastatic site is the skeleton, but other distant organs including brain, lungs and liver are also affected. Secondary disease, particularly skeletal metastasis, can develop decades after the detection and treatment of the primary tumour.

Bone metastases are associated with major complications such as hypercalcaemia, pathological fractures and spinal cord compression, resulting in a considerable reduction in quality of life. Although the focus of intensive research, the mechanisms initiating the metastatic process are not fully understood, and the lack of available patient bone biopsies containing tumour cells hampers the investigation of bone metastasis in humans.

The development of metastasis in distant organs is a multistep process that begins with the detachment of cancer cells from the primary tumour, via their invasion of the extra-cellular matrix, entry into the blood stream and the eventual colonisation and outgrowth at secondary sites. However, only a small proportion of the cells that escape from the primary tumour will successfully colonise a distant organ, with the majority of circulating tumour cells (CTCs) being recognised and eliminated by the immune system, undergoing spontaneous apoptosis or re-entering the blood stream and potentially colonising other organs.

Bone metastasis have focused on advanced stages of cancer-induced disease, where the micro- or macro-metastases are already established. In contrast, much less information is available regarding the early stages of breast cancer bone colonisation, when tumour cells remain in a dormant state within the bone marrow. Cells of the osteoblastic lineage are reported to be involved in the tumour establishment and progression of bone metastases in pre-clinical models of both breast and prostate cancer.

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Journal of Orthopedic Oncology