Studying biomineralization pathways in a 3D culture model of breast cancer microcalcifications.

Studying biomineralization pathways in a 3D culture model of breast cancer microcalcifications.
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研究乳腺癌微钙化 3D 培养模型中的生物矿化途径。

DOI:
10.1016/j.biomaterials.2018.06.030
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发表时间:
2018
期刊:
影响因子:
14
通讯作者:
Estroff,LaraA
Estroff,LaraA
中科院分区:
工程技术1区
文献类型:
--
作者:
Vidavsky,Netta;Kunitake,JennieAmr;Chiou,AaronE;Northrup,PaulA;Porri,TeresaJ;Ling,Lu;Fischbach,Claudia;Estroff,LaraA

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微钙化作为乳腺癌的诊断标志物,但其形成途径和在癌症进展中的作用存在争议,部分原因是缺乏相关的3D培养模型,可以研究细胞对矿化的调节程度。以前的研究表明,从与细胞死亡相关的营养不良性矿化到骨样矿物质沉积的过程。在这里,我们评估了3D多细胞球体中的微钙化形成,这些球体由MCF 10A人类乳腺肿瘤进展系列中的非恶性、癌前和侵袭性细胞系生成。具有更大恶性潜能的球状体发展为坏死核心,从而重现了已知调节肿瘤体内细胞行为的空间上不同的活性和非活性区域。使用nanoCT、电子显微镜和X射线光谱对微钙化的空间分布及其组成进行了表征。磷灰石微钙化主要在活细胞区域内检测到,它们的数量和大小随着球体的恶性潜能而增加。碱性磷酸酶水平随着恶性潜能的降低而降低,而骨桥蛋白水平则升高。这些发现支持了一种矿化途径,其中癌细胞以与其恶性潜能相关的方式诱导矿化,但与生理性成骨矿化不同。
Microcalcifications serve as diagnostic markers for breast cancer, yet their formation pathway(s) and role in cancer progression are debated due in part to a lack of relevant 3D culture models that allow studying the extent of cellular regulation over mineralization. Previous studies have suggested processes ranging from dystrophic mineralization associated with cell death to bone-like mineral deposition. Here, we evaluated microcalcification formation in 3D multicellular spheroids, generated from non-malignant, pre-cancer, and invasive cell lines from the MCF10A human breast tumor progression series. The spheroids with greater malignancy potential developed necrotic cores, thus recapitulating spatially distinct viable and non-viable areas known to regulate cellular behavior in tumorsin vivo. The spatial distribution of the microcalcifications, as well as their compositions, were characterized using nanoCT, electron-microscopy, and X-ray spectroscopy. Apatite microcalcifications were primarily detected within the viable cell regions and their number and size increased with malignancy potential of the spheroids. Levels of alkaline phosphatase decreased with malignancy potential, whereas levels of osteopontin increased. These findings support a mineralization pathway in which cancer cells induce mineralization in a manner that is linked to their malignancy potential, but that is distinct from physiological osteogenic mineralization.
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DOI: --
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DOI: --
发表时间: 1982
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