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Diffuse osteosclerosis as a presentation of recurrent breast cancer: role of endothelin 1

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Abstract

Summary

We report a 46-yr-old woman with a history of breast cancer who presented with diffuse myalgias, bone pain, and osteosclerosis. She was found to have recurrent breast cancer producing endothelin-1.

Introduction

Acquired osteosclerosis can be caused by various disorders. Endothelin -1 is believed to contribute to osteosclerosis caused by breast cancer.

Methods

Although the bone marrow biopsy did not reveal breast cancer, she developed skin lesions consistent with metastatic breast cancer. She ultimately died from progressive disease. At autopsy immunohistochemistry for endothelin-1 was performed on a section from the L5 vertebral body.

Results

The section from the L5 vertebral body showed small foci of cells consistent with metastatic carcinoma and a prominent sclerotic response. Immunohistochemistry for endothelin-1 was strongly positive.

Conclusions

Recurrent breast cancer may present with diffuse osteosclerosis. Endothelin-1 may be a paracrine factor responsible for increased bone formation and osteosclerosis.

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References

  1. Rosol TJ (2000) Pathogenesis of bone metastases: role of tumor related proteins. J Bone Miner Res 15:844–850

    Article  CAS  PubMed  Google Scholar 

  2. Eck L, Graves L III, Lukert B, Bhattacharya (2008) Sclerotic bone changes on densitometry testing in a patient with a remote history of breast cancer. Endocr Pract 14(1):125–126

    Article  PubMed  Google Scholar 

  3. Guise TA, Mundy GR (1998) Cancer and bone. Endocr Rev 19(1):18–54. https://doi.org/10.1210/edrv.19.1.0323

    Article  CAS  PubMed  Google Scholar 

  4. Achbarou A, Kaiser S, Tremblay G, Ste-Marie LG, Brodt P, Goltzman D, Rabbani SA (1994) Urokinase overproduction results in increased skeletal metastasis by prostate cancer cells in vivo. Cancer Res 54(9):2372–2377

    CAS  PubMed  Google Scholar 

  5. Thalmann GN, Anezinis PE, Chang SM, Zhau HE, Kim EE, Hopwood VL, Pathak S, con Eschenbach AC, Chung LW (1994) Androgen-independent cancer progression and bone metastasis in the LNCaP model of human prostate cancer. Cancer Res 54:2577–2581

    CAS  PubMed  Google Scholar 

  6. Gingrich JR, Barrios RJ, Morton RA, Boyce BF, DeMayo FJ, Finegold MJ, Angelopoulou R, Rosen JM, Greenberg NM (1996) Metastatic prostate cancer in a transgenic mouse. Cancer Res 56:4096–4102

    CAS  PubMed  Google Scholar 

  7. Nelson JB, Chan-Tach K, Hedican SP, Magnuson SR, Opgenorth TJ, , Bova GS, & Simons JW. Endothelin-1 production and decreased endothelin B receptor expression in advanced prostate Cancer (1996) Cancer Res 56, 663–668

    CAS  PubMed  Google Scholar 

  8. Nelson JB, Hedican SP, Geroge DJ, Reddi AH, Piantadosi S, Eisenberger AA, Simons JW (1995) Identification of endothelin–1 in the pathophysiology of metastatic adenocarcinoma of the prostate. Nat Med 1:944–949

    Article  CAS  PubMed  Google Scholar 

  9. Nelson JB, Nguyne SH, Wu-Wong JR, Opgenorth TJ, Dixon DB, Chung LW, Inoue N (1999) New bone formation in an osteoblastic tumor model is increased by endothelin-1 overexpression and decreased by endothelin a receptor blockade. Urology 53:1063–1069

    Article  CAS  PubMed  Google Scholar 

  10. Davenport AP, Hyndman KA, Dhaun N, Southan C, Kohan DE, Pollock JS, Pollock DM, Webb DJ, Maguire JJ (2016 Apr) Endothelin. Pharmacol Rev 68(2):357–418. https://doi.org/10.1124/pr.115.011833

    Article  PubMed  PubMed Central  Google Scholar 

  11. Rosanò L, Spinella F, Bagnato A (2013) Endothelin 1 in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer 13(9):637–651. https://doi.org/10.1038/nrc3546

    Article  CAS  PubMed  Google Scholar 

  12. Guise TA (2003) A causual role for endothelin-1 in the pathogenesis of osteoblastic bone metastases. PNAS 100(19):10954–10959

    Article  CAS  PubMed  Google Scholar 

  13. Tamkus D, Sikorskii A, Gallo K, Wiese D, Leece C, Madhukar B, Chivu S, Chitneni S, Dimitrov N (2013) Endothelin-1 enriched tumor phenotype predicts breast cancer recurrence. ISRN Oncol 2013:7

    Google Scholar 

  14. Kedzierski RM, Yanagisawa M (2001) Endothelin system: the double-edged sword in health and disease. Annu Rev Pharmacol Toxicol 41:851–876

    Article  CAS  PubMed  Google Scholar 

  15. Malek AM, Greene AL, Izumo S (1993) Regulation of endothelin 1 gene by fluid shear stress is transcriptionally mediated and independent of protein kinase C and cAMP. Proc Natl Acad Sci U S A 90:5999–6003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Xu D, Emoto N, Giaid A, Slaughter C, Kaw S, deWit D, Yanagisawa M (1994) ECE-1: a membrane-bound metalloprotease that catalyzes the proteolytic activation of big endothelin-1. Cell 78:473–485

    Article  CAS  PubMed  Google Scholar 

  17. Wolff K, Nisell H, Carlström K, Kublickiene K, Hemsén A, Lunell N-O, Lindblom B (1996) Endothelin-1 and big endothelin-1 levels in normal term pregnancy and in preeclampsia. Regul Pept 67(3):211–216. https://doi.org/10.1016/s0167-0115(96)00122-x

    Article  CAS  PubMed  Google Scholar 

  18. Ken-Dror S, Weintraub Z, Yechiely H, Kahana L (2008) Atrial natriuretic peptide and endothelin concentrations in human milk during postpartum lactation. Acta Paediatr 86(8):793–795. https://doi.org/10.1111/j.1651-2227.1997.tb08599.x

    Article  Google Scholar 

  19. Clines G, Mohammad KS, Bao Y, Stephens O, Suva L, Shaughnessy JD, Fox JW, Chirgwin J, Guise T (2007) Dickkopf homolog 1 mediates Endothelin-1-stimulated new bone formation. Mol Endocrinol 21(2):486–498

    Article  CAS  PubMed  Google Scholar 

  20. Johnson MG, Kristianto J, Yuan B, Konicke K, Blank R (2014) Big endothelin changes the cellular miRNA environment in TMOb osteoblasts and increases mineralization. Connect Tissue Res 55(Suppl 1):113–116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Qi P, Chen M, Zhang LX, Song RX, He ZH, Wang ZP (2015) A meta-analysis and indirect comparison of endothelin a receptor antagonist for castration-resistant prostate cancer. PLoS One 10(7):e0133803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

Funded in part by NIH AR54753. www.nih.gov. (Robert Blank). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author information

Authors and Affiliations

  1. Department of Medicine (Endocrinology), Medical College of Wisconsin, Milwaukee, WI, USA

    K. G. Zarnecki, J. Kristianto, R. D. Blank & J. L. Shaker

  2. Department of Medicine (Endocrinology), University of Wisconsin School of Medicine, Madison, WI, USA

    J. Kristianto

  3. GRECC Service and William S. Middleton Veterans Hospital, Madison, WI, USA

    J. Kristianto & R. D. Blank

  4. Endocrine and Reproductive Physiology Program, University of Wisconsin, Madison, WI, USA

    J. Kristianto

  5. Unity Biotechnology, Brisbane, CA, USA

    J. Kristianto

  6. Department of Medicine (Hematology and Oncology), Medical College of Wisconsin, Milwaukee, WI, USA

    J. Charlson

  7. Department of Dermatology, Medical College of Wisconsin, Milwaukee, WI, USA

    B. Wilson

  8. Medical Service, Clement J. Zablocki VAMC, Milwaukee, WI, USA

    R. D. Blank

Authors
  1. K. G. Zarnecki
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  2. J. Kristianto
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  3. J. Charlson
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  4. B. Wilson
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  5. R. D. Blank
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  6. J. L. Shaker
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Corresponding author

Correspondence to J. L. Shaker.

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Conflict of interest

None directly related to this work, Jasmin Kristianto Employee: Unity Biotechnology John Charlson Advisory Board:Immune Design Clinical trial funding: Lilly Oncology Robert D. Blank Consultant: Amgen, Novo-Nordisk, Radius Health, Ultragenyx Authorship Royalties: UpToDate, McGraw-Hill Ownership Interest: JangoBio, Abbott Laboratories, Abbvie Joseph L. Shaker Consultant Shire, Alexion, Ultragenyx Authorship Royalties: McGraw-Hill.

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Zarnecki, K.G., Kristianto, J., Charlson, J. et al. Diffuse osteosclerosis as a presentation of recurrent breast cancer: role of endothelin 1. Osteoporos Int 30, 1699–1703 (2019). https://doi.org/10.1007/s00198-019-04998-5

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  • DOI: https://doi.org/10.1007/s00198-019-04998-5

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