Purpose of Review The purpose of this review is to explore the role of monocyte chemoattractant protein-1 (MCP-1 or CCL2) in the processes that underpin bone remodelling, particularly the action of osteoblasts and osteoclasts, and its role in the development and metastasis of cancers that target the bone. Recent Findings MCP-1 is a key mediator of osteoclastogenesis, being the highest induced gene during intermittent treatment with parathyroid hormone (iPTH), but also regulates catabolic effects of continuous PTH on bone including monocyte and macrophage recruitment, osteoclast formation and bone resorption. In concert with PTH-related protein (PTHrP), MCP-1 mediates the interaction between tumour-derived factors and host-derived chemokines to promote skeletal metastasis. In breast and prostate cancers, an osteolytic cascade is driven by tumour cell-derived PTHrP that upregulates MCP-1 in osteoblastic cells. This relationship between PTHrP and osteoblastic expression of MCP-1 may drive the colonisation of disseminated breast cancer cells in the bone. Summary There is mounting evidence to suggest a pivotal role of MCP-1 in many diseases and an important role in the establishment of comorbidities. Coupled with its role in bone remodelling and the regulation of bone turnover, there is the potential for pathological relationships between bone disorders and bone-related cancers driven by MCP-1. MCP-1's role in bone remodelling and bone-related cancers highlights its potential as a novel anti-resorptive and anti-metastatic target. Keywords MCP-1 or CCL-2. Breast cancer. Osteoclast. Bone remodelling. Metastasis This article is part of the Topical Collection on Skeletal Biology and Regulation

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BackgroundDistant relapse of breast cancer complicates management of the disease and accounts for 90% of breast cancer‐related deaths. Monocyte chemoattractant protein‐1 (MCP‐1) has critical roles in breast cancer progression and is widely accepted as a pro‐metastatic chemokine.MethodsThis study explored MCP‐1 expression in the primary tumour of 251 breast cancer patients. A simplified ‘histoscore’ was used to determine if each tumour had high or low expression of MCP‐1. Patient breast cancers were retrospectively staged based on available patient data. p < 0.05 was used to determine significance and changes in hazard ratios between models were considered.ResultsLow MCP‐1 expression in the primary tumour was associated with breast cancer‐related death with distant relapse in ER− breast cancers (p < 0.01); however, this was likely a result of most low MCP‐1‐expressing ER− breast cancers being Stage III or Stage IV, with high MCP‐1 expression in the primary tumour significantly correlated with Stage I breast cancers (p < 0.05). Expression of MCP‐1 in the primary ER− tumours varied across Stage I, II, III and IV and we highlighted a switch in MCP‐1 expression from high in Stage I ER− cancers to low in Stage IV ER− cancers.ConclusionThis study has emphasised a critical need for further investigation into MCP‐1's role in breast cancer progression and improved characterisation of MCP‐1 in breast cancers, particularly in light of the development of anti‐MCP‐1, anti‐metastatic therapies.

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