Mechanobiology of Bone Metastatic Cancer

Temporal and spatial changes in bone mineral content and mechanical properties during breast-cancer bone metastases

“…This study reported reduced migration and increased apoptosis of these breast cancer cells, compared to non-mechanically stimulated osteocyte conditioned media ( Ma et al, 2018 ). These findings are reflected in previous human and animal studies where exercise or direct mechanical loading regimes of long bones inhibit tumour progression, proposedly due to altered TGF-β signaling and sclerostin secretion in mechanosensitive osteocytes ( Sarazin et al, 2021 ). Notably, a study of MDA-MB231 breast cancer cell-inoculated proximal tibiae, in SCID mice subjected to dynamic compressive loads for 6 weeks, reported inhibited osteolytic progression, via limited loss of bone volume and trabecular thickness, during metastasis suggested to be a result of mechanoregulation of osteoblast and osteoclast activity ( Lynch et al, 2013 ).…”

Practical factors that influence physical activity in women living with metastatic breast cancer: a qualitative interview study

“…Consistent with population rates of site occurrence (18), a number of participants reported speci c issues related to bone metastases, particularly in the axial and hip bones. Pre-clinical ndings have established that mechanical loading with exercise can reverse metastatic disease-induced bone loss (19), but navigating pain and fracture risk to translate this to practice is intimidating for both patients and clinicians (20,21,22). In response, recent international efforts have taken place to garner consensus for recommendations and preliminary guidelines (23).…”

Role of the osteocyte in bone metastasis – The importance of networking

“…This is likely due to the complexity of the intracellular signalling networks, and thus recent in vitro studies have attempted to further unpick this relationship. There is much conflicting evidence in the literature on the effect of mechanical stimulation [1] , [10] , with some studies finding that mechanical stimulation of osteocytes increases migration of breast cancer cells [19] , [20] , and others showing decreased migration/invasion [21] , [22] , [23] . Recent advances in the use of in vitro studies to identify the likely mechanobiological molecular mechanisms involved are discussed in detail in this section.…”

“…Separately, much work on the effect of breast cancer cells on osteocyte mechano-sensitivity has been carried out by the Lynch group [10] , demonstrating that mechanical loading of breast cancer cells produces factors that reduce both osteocyte dendrite formation and bone resorption downstream of osteocytes [29] . Building on this work, they recently showed using an in vitro scaffold loading model that breast cancer cells can directly impair the mechano-sensitivity of osteocytes using soluble signals in conditioned media [30] .…”

“…A number of excellent reviews of have delved into the detail of the osteocyte’s interactions in the microenvironment of various metastatic cancers affecting bone [5] , [6] , as well as its potential role in the cellular origins of osteosarcoma [1] . These in-depth reviews are listed for further reading in Table 1 , alongside a number of other articles that explain what is known about the vicious cycle [1] , [5] , [6] , [7] , osteocyte biology and mechanobiology [2] , [3] , [4] , the role of osteoblasts and osteoclasts in metastasis [8] , [9] , [10] , [11] , and the bone remodelling cycle [12] . This perspective instead shines a spotlight on key recent findings in the last 5 years that underline emerging role of the osteocyte as the central cell in a complex network of signalling crosstalk in the metastatic microenvironment.…”