Abstract
Bone morphogenetic proteins (BMPs) belong to the TGF-β super family, and are essential for the regulation of foetal development, tissue differentiation and homeostasis and a multitude of cellular functions. Naturally, this has led to the exploration of aberrance in this highly regulated system as a key factor in tumourigenesis. Originally identified for their role in osteogenesis and bone turnover, attention has been turned to the potential role of BMPs in tumour metastases to, and progression within, the bone niche. This is particularly pertinent to breast cancer, which commonly metastasises to bone, and in which studies have revealed aberrations of both BMP expression and signalling, which correlate clinically with breast cancer progression. Ultimately a BMP profile could provide new prognostic disease markers. As the evidence suggests a role for BMPs in regulating breast tumour cellular function, in particular interactions with tumour stroma and the bone metastatic microenvironment, there may be novel therapeutic potential in targeting BMP signalling in breast cancer. This review provides an update on the current knowledge of BMP abnormalities and their implication in the development and progression of breast cancer, particularly in the disease-specific bone metastasis.
Highlights
Breast cancer is the most common cancer in women worldwide (Ferlay et al 2015)
Bone morphogenetic proteins (BMPs)- 6 reporter activity increased with anti-oestrogen treatment, and decreased with oestradiol treatment, providing evidence that ER regulates BMP-6 differentially in breast and bone, and ERα-dependent pathways may influence skeletal secondary formation in breast cancer, which is consistent with the previous observation that patients with ER positive breast tumours are more likely to develop skeletal metastases (Ong et al 2004)
Aberrant expression of BMPs and BMP signalling has been implicated in breast cancer and disease-specific bone metastasis
Summary
Breast cancer is the most common cancer in women worldwide (Ferlay et al 2015). In developed countries, it receives media coverage and research funding above all other cancers (Konfortion et al 2014, American Cancer Society 2016) and continual progress is made in understanding tumour biology, developing diagnostics and improved therapeutics. BMP-2 under routine culture conditions, shows proapoptotic effect in MCF-7 breast cancer cells, in which the expression and function of apoptosis related genes, protein kinase R (PKR), and subsequent activation of its substrate eIF2α are regulated by BMP signalling (Steinert et al 2008). Another potentially bidirectional BMP, both increased and decreased BMP-7 expression in primary breast tumours has been correlated with disease-specific bone metastases (Buijs et al 2007, Alarmo et al 2008).
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