Bone Endosteal Mimics Regulates Breast Cancer Development and Phenotype.

Bone is a frequent site for metastatic development in various cancer types, including breast cancer, with a grim prognosis due to the distinct bone environment. Despite considerable advances, our understanding of the underlying processes leading to bone metastasis progression remains elusive. Here, we applied a bioactive three-dimensional (3D) model capable of mimicking the endosteal bone microenvironment. MDA-MB-231 and MCF7 breast cancer cells were cultured on the scaffolds, and their behaviors and the effects of the biomaterial on the cells were examined over time. We demonstrated that close interactions between the cells and the biomaterial affect their proliferation rates and the expression of c-Myc, cyclin D, and KI67, leading to cell cycle arrest. Moreover, invasion assays revealed increased invasiveness within this microenvironment. Our findings suggest a dual role for endosteal mimicking signals, influencing cell fate and potentially acting as a double-edged sword, shuttling between cell cycle arrest and more active, aggressive states.

Review old bone, new tricks.

Despite the significant progress made over the past decade with combination of molecular profiling data and the development of new clinical strategies, our understanding of metastasis remains elusive. Bone metastasis is a complex process and a major cause of mortality in breast and prostate cancer patients, for which there is no effective treatment to-date. The current review summarizes the routes taken by the metastatic cells and the interactions between them and the bone microenvironment. We emphasize the role of the specified niches and cues that promote cellular adhesion, colonization, prolonged dormancy, and reactivation. Understanding these mechanisms will provide better insights for future studies and treatment strategies for bone metastatic conditions.

Characteristics of pre-metastatic niche: the landscape of molecular and cellular pathways.

Metastasis is a major contributor to cancer-associated deaths. It involves complex interactions between primary tumorigenic sites and future metastatic sites. Accumulation studies have revealed that tumour metastasis is not a disorderly spontaneous incident but the climax of a series of sequential and dynamic events including the development of a pre-metastatic niche (PMN) suitable for a subpopulation of tumour cells to colonize and develop into metastases. A deep understanding of the formation, characteristics and function of the PMN is required for developing new therapeutic strategies to treat tumour patients. It is rapidly becoming evident that therapies targeting PMN may be successful in averting tumour metastasis at an early stage. This review highlights the key components and main characteristics of the PMN and describes potential therapeutic strategies, providing a promising foundation for future studies.