Microcalcifications in breast cancer: novel insights into the molecular mechanism and functional consequence of mammary mineralisation.
Microcalcifications in breast cancer: novel insights into the molecular mechanism and functional consequence of mammary mineralisation.
复制标题
DOI：
10.1038/bjc.2011.583
复制
发表时间：
2012-01-31
影响因子：
8.8
通讯作者：
Morgan, M. P.
中科院分区：
文献类型：
--
作者：
Cox, R. F.;Hernandez-Santana, A.;Ramdass, S.;McMahon, G.;Harmey, J. H.;Morgan, M. P.
乳房X线照相微钙化代表了不可触及的乳腺癌最可靠的特征之一，但在很大程度上仍未被探索和了解。我们报告了一种新模型来研究一组乳腺细胞系的体外矿化潜力。通过将致瘤细胞植入雌性 BALB/c 小鼠的乳腺脂肪垫中产生原发性乳腺肿瘤。羟基磷灰石（HA）仅由致瘤细胞系沉积，表明矿化潜力可能与该体外模型中的细胞表型相关。我们提出了一种乳腺矿化机制，这表明生理矿化的增强剂和抑制剂之间的平衡被破坏。碱性磷酸酶和磷酸盐转运的抑制阻止了矿化，表明矿化是一个活跃的细胞介导的过程。研究发现羟基磷灰石可以增强体外肿瘤细胞的迁移，而草酸钙则没有效果，这凸显了钙沉积的潜在后果。此外，HA还沉积在将致瘤细胞植入雌性BALB/c小鼠的乳腺脂肪垫中产生的原发性乳腺肿瘤中。这项工作表明乳腺 HA 的形成是一个细胞特异性的调节过程，它创造了一个可能促进乳腺肿瘤进展的仿骨生态位。我们的研究结果指出细胞矿化潜力和调节它的微环境是乳腺肿瘤发展的一个重要特征。
Mammographic microcalcifications represent one of the most reliable features of nonpalpable breast cancer yet remain largely unexplored and poorly understood. We report a novel model to investigate the in vitro mineralisation potential of a panel of mammary cell lines. Primary mammary tumours were produced by implanting tumourigenic cells into the mammary fat pads of female BALB/c mice. Hydroxyapatite (HA) was deposited only by the tumourigenic cell lines, indicating mineralisation potential may be associated with cell phenotype in this in vitro model. We propose a mechanism for mammary mineralisation, which suggests that the balance between enhancers and inhibitors of physiological mineralisation are disrupted. Inhibition of alkaline phosphatase and phosphate transport prevented mineralisation, demonstrating that mineralisation is an active cell-mediated process. Hydroxyapatite was found to enhance in vitro tumour cell migration, while calcium oxalate had no effect, highlighting potential consequences of calcium deposition. In addition, HA was also deposited in primary mammary tumours produced by implanting the tumourigenic cells into the mammary fat pads of female BALB/c mice. This work indicates that formation of mammary HA is a cell-specific regulated process, which creates an osteomimetic niche potentially enhancing breast tumour progression. Our findings point to the cells mineralisation potential and the microenvironment regulating it, as a significant feature of breast tumour development.
登录
查看更多内容
影响因子：
4.8
作者：
Lian, JB;Shalhoub, V;Stein, JL
通讯作者：
Stein, JL
影响因子：
3.3
作者：
FRAPPART, L;BOUDEULLE, M;FEROLDI, J
通讯作者：
FEROLDI, J
影响因子：
4.2
作者：
Gericke, A;Qin, C;Boskey, AL
通讯作者：
Boskey, AL
影响因子：
2.9
作者：
Keykhosravani, M;Doherty-Kirby, A;Lajoie, G
通讯作者：
Lajoie, G
影响因子：
4.8
作者：
Addison, William N.;Azari, Fereshteh;McKee, Marc D.
通讯作者：
McKee, Marc D.