当前位置： SCI文献检索 > JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH期刊下所有文献 > RANKL/RANK/OPG system beyond bone remodeling: involvement in breast cancer and clinical perspectives.

RANKL/RANK/OPG system beyond bone remodeling: involvement in breast cancer and clinical perspectives.

Abstract：

:RANKL/RANK/OPG system consists of three essential signaling molecules: i) the receptor activator of nuclear factor (NF)-kB-ligand (RANKL), ii) the receptor activator of NF-kB (RANK), and iii) the soluble decoy receptor osteoprotegerin (OPG). Although this system is critical for the regulation of osteoclast differentiation/activation and calcium release from the skeleton, different studies have elucidated its specific role in mammary gland physiology and hormone-driven epithelial proliferation during pregnancy. Of note, several data suggest that progesterone induces mammary RANKL expression in mice and humans. In turn, RANKL controls cell proliferation in breast epithelium under physiological conditions typically associated with higher serum progesterone levels, such as luteal phase of the menstrual cycle and pregnancy. Hence, RANKL/RANK system can be regarded as a major downstream mediator of progesterone-driven mammary epithelial cells proliferation, potentially contributing to breast cancer initiation and progression. Expression of RANKL, RANK, and OPG has been detected in breast cancer cell lines and in human primary breast cancers. To date, dysregulation of RANKL/RANK/OPG system at the skeletal level has been widely documented in the context of metastatic bone disease. In fact, RANKL inhibition through the RANKL-blocking human monoclonal antibody denosumab represents a well-established therapeutic option to prevent skeletal-related events in metastatic bone disease and adjuvant therapy-induced bone loss in breast cancer. On the other hand, the exact role of OPG in breast tumorigenesis is still unclear. This review focuses on molecular mechanisms linking RANKL/RANK/OPG system to mammary tumorigenesis, highlighting pre-clinical and clinical evidence for the potential efficacy of RANKL inhibition as a prevention strategy and adjuvant therapy in breast cancer settings.

journal_name

J Exp Clin Cancer Res

journal_title

Journal of experimental & clinical cancer research : CR

authors

Infante M,Fabi A,Cognetti F,Gorini S,Caprio M,Fabbri A

doi

10.1186/s13046-018-1001-2

subject

Has Abstract

pub_date

2019-01-08 00:00:00

pages

issue

eissn

0392-9078

issn

1756-9966

pii

10.1186/s13046-018-1001-2

journal_volume

pub_type

杂志文章,评审

在线工具

RANKL/RANK/OPG system beyond bone remodeling: involvement in breast cancer and clinical perspectives.