Bone metastasis in endocrine-related cancer: unravelling invasion and destruction

in Endocrine-Related Cancer
Authors:
Huong Q Duong School of Health, University of the Sunshine Coast, Sippy Downs, Queensland, Australia

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Georgia Kafer School of Health, University of the Sunshine Coast, Sippy Downs, Queensland, Australia

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, and
Michelle Maugham-Macan School of Health, University of the Sunshine Coast, Sippy Downs, Queensland, Australia

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https://orcid.org/0000-0001-5775-5162

Correspondence should be addressed to M Maugham-Macan: mmaughammacan@usc.edu.au

This paper is part of a special collection highlighting the work of emerging leaders in the endocrine cancer field.

DOI:
https://doi.org/10.1530/ERC-24-0294
Volume/Issue:
Volume 32: Issue 2
Article Type:
Review Article
Article ID:
e240294
Online Publication Date:
11 Jan 2025
Copyright:
© the author(s) 2025
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Bone is a common and debilitating site for metastatic cancer cell expansion. Skeletal metastasis is a multistage process, with primary stages of circulating tumour cells, progressing to a dormant state in vasculature and bone marrow niches, followed by tumourigenic reactivation, proliferation and finally bone destruction. The frequency of bone metastasis is reconciled in Paget’s ‘seed and soil’ hypothesis, where a conducive microenvironment (bone niche) is essential for cancer cell colonisation. Cancer cells can mimic bone cells (osteomimicry) and interact with the bone marrow’s vascular architecture, utilising pathways akin to haematopoietic stem cell expansion. Current research suggests that each phase of bone metastasis is associated with specific gene expression and protein abundance patterns. For example, E-selectin, CXCR-4 and CXCL-12 are crucial for cancer cell homing, dormancy and colonisation of bone tissue. In contrast, different primary cancers appear to have unique staging profiles. In prostate cancer, dormancy is modulated by the CXCR-4/CXCL-12, ANXA2/CXCL12 and GAS6 pathways, while in breast cancer, dormancy involves ERK1/2, p38, MSK1, LIF, BMP-7, TGF-β1/2 and bone resorption factors. Conversely, osteoblastic metastasis in both breast and prostate cancers is characterised by ET-1, Dkk1 suppression and the release of IL-6, MCP-1, VEGF, FGF and IGF, while osteolytic metastasis primarily depends on PTHrP, RANKL, OPG, TGF-β, IGF, TNF-α, IL-1 and IL-7. Understanding the complex molecular mechanisms facilitating cancer cell colonisation and expansion in bone tissues is essential for developing effective treatments to prevent bone metastases. In this review, we discuss current theories linking bone remodelling with bone.

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Print ISSN:
1351-0088
Online ISSN:
1479-6821
Copyright:
© the author(s) 2025
Article ID:
e240294
Received Date:
07 Nov 2024
Rev-recd:
09 Dec 2024
Accepted Date:
19 Dec 2024
Print Publication Date:
01 Feb 2025
Online Publication Date:
11 Jan 2025
Keywords:
bone metastasis; EMT; bone remodelling; bone colonisation; osteoblastic; osteolytic

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