Center for Applied Tissue Engineering and Regenerative Medicine (CANTER), Munich University of Applied Sciences, Munich, Germany.
Chair of Applied Physics, Ludwig-Maximilians-Universität, Munich, Germany.
PLoS One. 2020 Aug 28;15(8):e0237116. doi: 10.1371/journal.pone.0237116. eCollection 2020.
Bone metastases are a frequent complication in prostate cancer, and several studies have shown that vitamin D deficiency promotes bone metastases. However, while many studies focus on vitamin D's role in cell metabolism, the effect of chronically low vitamin D levels on bone tissue, i.e. insufficient mineralization of the tissue, has largely been ignored. To investigate, whether poor tissue mineralization promotes cancer cell attachment, we used a fluorescence based adhesion assay and single cell force spectroscopy to quantify the adhesion of two prostate cancer cell lines to well-mineralized and demineralized dentin, serving as biomimetic bone model system. Adhesion rates of bone metastases-derived PC3 cells increased significantly on demineralized dentin. Additionally, on mineralized dentin, PC3 cells adhered mainly via membrane anchored surface receptors, while on demineralized dentin, they adhered via cytoskeleton-anchored transmembrane receptors, pointing to an interaction via exposed collagen fibrils. The adhesion rate of lymph node derived LNCaP cells on the other hand is significantly lower than that of PC3 and not predominately mediated by cytoskeleton-linked receptors. This indicates that poor tissue mineralization facilitates the adhesion of invasive cancer cells by the exposure of collagen and emphasizes the disease modifying effect of sufficient vitamin D for cancer patients.
骨转移是前列腺癌的常见并发症，多项研究表明维生素 D 缺乏会促进骨转移。然而，虽然许多研究都集中在维生素 D 对细胞代谢的作用上，但慢性低维生素 D 水平对骨组织的影响，即组织矿化不足，在很大程度上被忽视了。为了研究组织矿化不良是否促进癌细胞黏附，我们使用基于荧光的黏附测定法和单细胞力谱法，来定量两种前列腺癌细胞系与矿化良好和脱矿的牙本质（作为仿生骨模型系统）的黏附。骨转移衍生的 PC3 细胞在脱矿牙本质上的黏附率显著增加。此外，在矿化牙本质上，PC3 细胞主要通过膜锚定的表面受体黏附，而在脱矿牙本质上，它们通过细胞骨架锚定的跨膜受体黏附，表明通过暴露的胶原纤维相互作用。另一方面，来自淋巴结的 LNCaP 细胞的黏附率明显低于 PC3 细胞，并且不是主要通过细胞骨架连接的受体介导。这表明组织矿化不良通过暴露胶原促进侵袭性癌细胞的黏附，并强调了充足的维生素 D 对癌症患者的疾病修饰作用。
