Multicellular spheroids containing synthetic mineral particles: an advanced 3D tumor model system to investigate breast precancer malignancy potential according to the mineral type

Abstract

Mineral particles that form in soft tissues in association with disease conditions are heterogeneous in their composition and physiochemical properties. Hence, it is challenging to study the effect of mineral...

Inhibiting Pathological Calcium Phosphate Mineralization: Implications for Disease Progression

“…Another variant examined was S-HA, which consists of spherical nanocrystalline HA particles. Unlike previous findings, S-HA did not stimulate cell proliferation, whether presented as individual particles or as aggregates . These differences can likely be attributed to differences in cell-to-mineral ratios, underscoring the need for meticulous consideration of experimental conditions when investigating cell-mineral interactions.…”

“…Previous in vitro studies have shown that exposure to HA in 2D cell culture systems can lead to increased cellular mitogenesis, proliferation rates, enhanced cell adhesion, upregulated matrix metalloproteinase activity, and elevated secretion of pro-osteoclastic interleukin-8 (IL-8). ,− Additionally, exposure to HA crystals has resulted in the enlargement of multicellular spheroids resembling tumor-like structures and increased Her2 expression in precancerous breast cells . In this study, we examined six distinct minerals as CaP analogues to assess their impact on the proliferation of DCIS cells.…”

“…Pathological calcifications have been linked to various health conditions such as renal and cardiovascular disorders, inflammation, and cancer. − In particular, in breast and thyroid cancers, microcalcifications (MCs) have been linked to increased malignancy and poorer prognosis. ,− These MCs primarily comprise calcium phosphate (CaP) minerals, mainly carbonated hydroxyapatite (HA). − In vitro studies have demonstrated that breast cancer cells exposed to HA crystals exhibit enhanced malignancy behavior, suggesting a potential connection between inhibiting crystallization and suppressing the progression of precancerous conditions. − The crystallization of MCs typically occurs within the extracellular matrix (ECM), an environment in which the surrounding fluid, such as blood, is expected to be supersaturated with respect to HA. ,,, Under normal physiological conditions, certain mineralization inhibitors found in ECM fluids play a pivotal role in inhibiting MC formation. − Developing a solution that mimics the properties of blood-like ECM fluid can provide a valuable platform for both investigating and controlling the crystallization of CaP in the tumor microenvironment. Simulated body fluids (SBFs) initially introduced by Kokubo et al have been extensively studied for biomimetic apatite formation and derived biomaterials. − SBFs are designed to mimic the physiochemical properties of blood serum, include inorganic ions, and maintain a pH of 7.4 at 37 °C.…”

Toward morphologically relevant extracellular matrix: nanofiber-hydrogel composites for tumor cell culture

“…Reliable in vitro cancer models are often considered powerful tools for studying the mechanisms of cancer development, assessing the efficacy of new drugs and understanding potential approaches to cancer treatment. 1,2 The demand for three-dimensional (3D) in vitro models is steadily increasing, driven by the necessity to capture the intricate complexity of tumor biology and drug development more effectively compared to traditional two-dimensional (2D) cultures. 2,3 3D culture systems provide a more realistic biochemical and biomechanical microenvironment, offering not only a comprehensive overview of tumor cell signaling in vivo but also enabling faithful reproduction of human tumor cell-matrix interactions in vitro .…”

“…1,2 The demand for three-dimensional (3D) in vitro models is steadily increasing, driven by the necessity to capture the intricate complexity of tumor biology and drug development more effectively compared to traditional two-dimensional (2D) cultures. 2,3 3D culture systems provide a more realistic biochemical and biomechanical microenvironment, offering not only a comprehensive overview of tumor cell signaling in vivo but also enabling faithful reproduction of human tumor cell-matrix interactions in vitro . 4 Individual tumor cells integrate numerous external cues, including those from various extracellular matrix (ECM) structures, components, mechanical stimuli, and soluble signals from neighboring or distant cells, to generate their fundamental phenotype and adapt to changes in the microenvironment.…”