Abstract
Cancer can disrupt the microenvironments and mechanical homeostatic actions in multiple scales from large tissue modification to altered cellular signaling pathway in mechanotransduction. In this review, we highlight recent progresses in breast cancer cell mechanobiology focusing on cell-microenvironment interaction and mechanical loading regulation of cells. First, the effects of microenvironmental cues on breast cancer cell progression and metastasis will be reviewed with respect to substrate stiffness, chemical/topographic substrate patterning, and 2D vs. 3D cultures. Then, the role of mechanical loading situations such as tensile stretch, compression, and flow-induced shear will be discussed in relation to breast cancer cell mechanobiology and metastasis prevention. Ultimately, the substrate microenvironment and mechanical signal will work together to control cancer cell progression and metastasis. The discussions on breast cancer cell responsiveness to mechanical signals, from static substrate and dynamic loading, and the mechanotransduction pathways involved will facilitate interdisciplinary knowledge transfer, enabling further insights into prognostic markers, mechanically mediated metastasis pathways for therapeutic targets, and model systems required to advance cancer mechanobiology.
Highlights
Breast cancer is the most diagnosed cancer among women in the US with significant mortality resulting from metastasis (DeSantis et al, 2019)
The mechanical factors may originate from microenvironments, e.g., extracellular matrix (ECM) stiffness, topography, composition, etc., as well as from dynamic mechanical loading situations, e.g., tensile strain, compression, flow-induced shear, etc
If osteocyte-derived conditioned medium and fluid flow-treated medium were given to breast cancer cells at 0.25 or 1 Pa shear stress, both media under lower shear stress resulted in mesenchymal-to-epithelial transition (MET) while flow-conditioned medium at high shear triggered epithelial-to-mesenchymal transition (EMT)
Summary
Breast cancer is the most diagnosed cancer among women in the US with significant mortality resulting from metastasis (DeSantis et al, 2019). Detection and prevention of breast cancer metastasis could greatly improve patient outcomes especially for cases when breast cancer migrates to crucial organs including brain, liver, lung, and bone. Mechanical factors are becoming more and more recognized as important regulators of oncogenesis, tumor progression, and metastasis. The mechanical factors may originate from microenvironments, e.g., extracellular matrix (ECM) stiffness, topography, composition, etc., as well as from dynamic mechanical loading situations, e.g., tensile strain, compression, flow-induced shear, etc. Microenvironmental factors at the premetastatic niche may prime tumor cells toward invasive phenotypes causing a host of genetic and mechanical adaptations, which can feedback to reinforce the aberrant ECM environment. Further adaptations accrue when tumor cells proliferate in a confined and stiffened ECM milieu
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