Abstract：
OBJECTIVE: This review discusses key oestrogens associated with the circulating pre- and post-menopausal milieu and how they may impact intratumoral oestrogen levels and breast cancer (BC) metastasis. It also identifies critical steps in BC metastasis to bone from the viewpoint of pigment epithelium-derived factor (PEDF) function, and discusses the role of several associated pro-metastatic biomarkers in BC bone metastasis.
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.
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.
摘要：
目的：这篇综述讨论了与绝经前后循环环境相关的关键雌激素，以及它们如何影响肿瘤内雌激素水平和乳腺癌（BC）转移。它还从色素上皮衍生因子（PEDF）功能的角度确定了BC转移到骨骼的关键步骤，并讨论了几种相关的促转移生物标志物在BC骨转移中的作用。
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。
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。
