Chemical and physical properties of carbonated hydroxyapatite affect breast cancer cell behavior

Abstract

Breast microcalcifications are routinely explored for mammographic detection of breast cancer and primarily composed of non-stoichiometric hydroxyapatite (Ca10-x(PO4)6-x(CO3)x(OH)2-x) (HA). Interestingly, HA morphology and carbonate substitution vary in malignant vs. benign lesions. However, whether or not these changes (i) are functionally linked and (ii) impact malignancy remains unclear due in part to a lack of model systems that permit evaluating these possibilities. Here, we have adapted a 96 well-based mineralized culture platform to investigate breast cancer cell behavior in response to systematic changes in the chemical and physical properties of HA. By adjusting the carbonate content of the simulated body fluid (SBF) solutions used during growth, we can control the morphology and carbonate substitution of the deposited HA. Our results suggest that both the combined and individual effects of these differences alter breast cancer cell growth and secretion of tumorigenic interleukin-8 (IL-8). Consequently, changes in both HA carbonate incorporation and morphology impact the behavior of breast cancer cells. Collectively, our data underline the importance of biomineralized culture platforms to evaluate the functional contribution of HA materials properties to the pathogenesis of breast cancer.

Synthesis and characterization of 159 Gd-doped hydroxyapatite nanorods for bioapplications as theranostic systems

“…The double bands at 1418 and 1479 cm À1 , observed only in the undoped sample, may be attributed to the presence of CO 3 2À , suggesting the formation of carbonated hydroxyapatite [41,42]. Carbonate ions can substitute either the phosphate group (type B) or the hydroxyl group (type A) in HA lattice [44].…”

Protein-crystal interface mediates cell adhesion and proangiogenic secretion

“…There has been increasing evidence that the nanoscale materials properties of bone apatite crystals likely modulate the pathogenesis of breast cancer bone metastasis [36–38]. Bone metastasis frequently occurs in patients at advanced stage of breast cancer and remains a major source of mortality in these patients [39].…”

“…The presence of HAP in mineralized tumor models increases tumor cell adhesion, proliferation, and secretion of both proangiogenic and proinflammatory factors [36]. Furthermore, HAP materials properties including particle size, crystallinity, carbonate incorporation, and morphology, all have combined and/or individual effects on protein adsorption and breast cancer cell behaviors [37,38,45]. However, synthetic HAP nanoparticles usually present multiple faces and tend to form agglomerates, which makes it difficult to deconvolute effects of face-specific surface chemistry and surface topography during interactions with ECM proteins and tumor cells.…”

Surface microtopography modulates sealing zone development in osteoclasts cultured on bone

“…In general, it was established that differences in the topography of adhesive surfaces can exert major effects on cell spreading [26], motility [27,28] and the formation of matrix adhesions [29,30]. In the context of bone remodelling, previous studies described the effect of surface topography on osteoclast differentiation [16], resorption activity [31] and SZ dimensions and dynamics [32].…”