RESULTS: PEDF is regulated by oestrogen in a number of oestrogen-sensitive tissues. Changes in circulating oestrogen levels associated with menopause may enhance the growth of BC bone metastases, leading to the establishment of a pre-metastatic niche. The establishment of such a pre-metastatic niche is driven by several key mediators, with pro-osteoclastic and pro-metastatic function which are upregulated by BC cells. These mediators appear to be regulated by oestrogen, as well as differentially affected by menopausal status. PEDF interacts with several pro-metastatic, pro-osteoclastic biomarkers, including C-X-C motif chemokine receptor 4 (CXCR4) and nuclear factor kappa B (NFκB) in BC bone metastasis.
CONCLUSIONS: Mediators such as CXCR4 and MT1-MMP underpin the ability of PEDF to function as an antimetastatic in other cancers such as osteosarcoma, highlighting the possibility that this serpin could be used as a therapeutic against BC metastasis in future.
结果:PEDF在许多雌激素敏感组织中受到雌激素调节。与绝经相关的循环雌激素水平的变化可能会增强BC骨转移的生长,导致转移前生态位的建立。这种转移前生态位的建立是由几个关键的中介驱动的,具有由BC细胞上调的促破骨细胞和促转移功能。这些介质似乎是由雌激素调节的,以及受更年期状况的不同影响。PEDF与几种前转移性相互作用,亲破骨细胞生物标志物,包括C-X-C基序趋化因子受体4(CXCR4)和核因子κB(NFκB)在BC骨转移中的作用。
结论:介体如CXCR4和MT1-MMP支持PEDF在其他癌症如骨肉瘤中发挥抗转移作用的能力,强调了这种serpin将来可以用作治疗BC转移的可能性。