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Breast cancer secreted factors alter the bone microenvironment

  • Chapter
Metastasis of Breast Cancer

Part of the book series: Cancer Metastasis – Biology and Treatment ((CMBT,volume 11))

Abstract

Bone is the most common site of breast cancer metastasis. Over eighty percent of patients with advanced breast cancer develop bone metastases. Once breast cancer has spread to bone, the cancer is incurable and patients develop mostly osteolytic, but also osteoblastic, or mixed bone lesions and suffer from extreme bone pain, skeletal fractures, hypercalcemia, and nerve compression. Current treatment is the use of antiresorptive bisphosphonates, which reduces bone pain and skeletal fractures but does not improve overall survival. Mouse models of bone metastasis have led to an understanding of the complex interactions that occur within bone that contribute to the incurability of the disease. Once breast cancer cells enter bone, a “vicious cycle” develops between breast cancer cells and the other cells within bone. Breast cancer cells secrete factors that stimulate bone cells, causing them in turn to secrete factors back onto the cancer cells. Inhibiting the actions of cancer-secreted factors may break this vicious cycle. The list of tumor-secreted factors is long, but they can be divided into three groups: (1) bone-resorbing, (2) bone-forming, and (3) metastasisopposing factors. These factors may share upstream regulatory pathways. Such central pathways could provide new targets for more effective treatment of bone metastasis. The TGF and hypoxia-induced Hif1 pathways are two leading targets for such adjuvant treatments.

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Authors and Affiliations

  1. Division of Endocrinology, University of Virginia, 801401, 22908-1401, Charlottesville, VA, USA

    Valerie A. Siclari

  2. Division of Endocrinology, University of Virginia, 801401, 22908-1401, Charlottesville, VA, USA

    Theresa A. Guise

  3. Division of Endocrinology, University of Virginia, 801401, 22908-1401, Charlottesville, VA, USA

    John M. Chirgwin PhD

Authors
  1. Valerie A. Siclari
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  2. Theresa A. Guise
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  3. John M. Chirgwin PhD
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Editors and Affiliations

  1. Department of Surgery, Cardiff University School of Medicine, Heath Park, CF14 4XN, Cardiff, UK

    Robert E. Mansel MS, FRCS, CBE

  2. Michell Cancer Institute, University of South Alabama, 307 N. University Blvd., 2015, 36688, AL, USA

    Oystein Fodstad PhD

  3. Metastasis and Angiogenesis Research Group, Cardiff University School of Medicine, CF14 4XN, Heath Park, Cardiff, UK

    Wen G. Jiang MB, BCh, MD

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© 2007 Springer

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Siclari, V.A., Guise, T.A., Chirgwin, J.M. (2007). Breast cancer secreted factors alter the bone microenvironment. In: Mansel, R.E., Fodstad, O., Jiang, W.G. (eds) Metastasis of Breast Cancer. Cancer Metastasis – Biology and Treatment, vol 11. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-5867-7_12

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