Zinc in microscopic calcifications isolated from thyroid fine needle aspiration may serve as a biomarker of thyroid nodule malignancy: A promising proof-of-concept

Inhibiting Pathological Calcium Phosphate Mineralization: Implications for Disease Progression

“…Without additives, transient ACP formed quickly and became carbonated HA within a day. Over 7 days, the Ca/P ratio of HA increased from 1.47 ± 0.06 to 1.67 ± 0.08, indicating a transformation from calcium-deficient apatite to a more stoichiometric form through structural rearrangements. − These HA minerals are submicrometer lumps with irregular spike-like surface textures, closely resembling those found in breast and thyroid cancer clinical samples. , Several trends emerged when additives were premixed with Ca 2+ in y-SBF. At an additive concentration of 100 μg mL –1 , there was no significant impact on HA mineralization for PAA.…”

“…48−50 These HA minerals are submicrometer lumps with irregular spike-like surface textures, closely resembling those found in breast and thyroid cancer clinical samples. 6,11 Several trends emerged when additives were premixed with Ca 2+ in y-SBF. At an additive concentration of 100 μg mL −1 , there was no significant impact on HA mineralization for PAA.…”

“…The analogues of ACP displayed unique characteristics: when in aggregate form, they unexpectedly enhanced cell proliferation in the order of S-ACP > M-ACP > C-ACP. This is significant as clinical samples often feature MCs in aggregate configurations. , Aggregates offer a substantial local surface area that plays a pivotal role in facilitating interactions with adjacent cells, promoting cell adhesion, affecting signaling, and serving as substantial substrates for cellular attachment. While individual small particles exhibit a higher surface-to-volume ratio than aggregates, the crux of the matter lies in the localized influence on cellular interactions.…”

“…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.…”

The interplay between crystallinity and the levels of Zn and carbonate in synthetic microcalcifications directs thyroid cell malignancy

“…Specifically, more than 90% of MCs originating from cancerous nodules contained Zn while most MCs from benign nodules lacked Zn. 19 Zn participates in numerous cellular processes, including cell signaling, proliferation, invasion, apoptosis, immune responses, and inflammation. [20][21][22] The correlation between the presence of Zn within thyroid FNA MCs and thyroid nodule malignancy can be interpreted through a few plausible avenues.…”