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Molecular insights into the interplay between adiposity, breast cancer and bone metastasis

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Abstract

Cancer is a complex disease, with various pre-existing health ailments enhancing its pathology. In cancer, the extracellular environment contains various intrinsic physiological factors whose levels are altered with aging and pre-existing conditions. In obesity, the tumor microenvironment and metastases are enriched with factors that are both derived locally, and from other physiological compartments. Similarly, in obesity, the cancer cell environment both at the site of origin and at the secondary site i.e., metastatic niche, contains significantly more phenotypically-altered adipocytes than that of un-obese cancer patients. Indeed, obesity has been linked with cancer progression, metastasis, and therapy resistance. Adipocytes not only interact with tumor cells, but also with adjacent stromal cells at primary and metastatic sites. This review emphasizes the importance of bidirectional interactions between adipocytes and breast tumor cells in breast cancer progression and its bone metastases. This paper not only chronicles the role of various adipocyte-derived factors in tumor growth, but also describes the significance of adipocyte-derived bone metastatic factors in the development of bone metastasis of breast cancer. It provides a molecular view of the interplay between the adipocytes and tumor cells involved in breast cancer bone metastasis. However, more research is needed to determine if targeting cancer-associated adipocytes holds promise as a potential therapeutic approach for breast cancer bone metastasis treatment.

Graphic abstract

Interplay between adipocytes and breast cancer cells at primary cancer site and metastatic bone microenvironment. AMSC Adipose-derived mesenchymal stem cell, CAA Cancer associated adipocytes, CAF Cancer associated fibroblast, BMSC Bone marrow derived mesenchymal stem cell, BMA Bone marrow adipocyte.

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Acknowledgements

Dr. Chandi C. Mandal is supported by the Department of Biotechnology [6242-P9/RGCB/PMD/DBT/CCML/2015], University Grant Commissions [30-49/2014 (BSR)] and Department of Science and Technology (India)-Russian Foundation for Basic Research (INT/RUS/RFBR/P-256). The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. We make an apology to various authors whose works could not be cited because of several limitations and space constraints.

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  1. Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, NH-8, Bandarsindri, Kishangarh, Ajmer, Rajasthan, 305817, India

    Sneha Soni & Chandi C. Mandal

  2. Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USA

    Meaghan Torvund

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SS had prepared tables, figures, and drafted manuscript. MT had re-organised and edited manuscript critically. CCM had formulated the manuscript and edited and contributed to the manuscript writing.

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Soni, S., Torvund, M. & Mandal, C.C. Molecular insights into the interplay between adiposity, breast cancer and bone metastasis. Clin Exp Metastasis 38, 119–138 (2021). https://doi.org/10.1007/s10585-021-10076-0

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