Skip to main content

Advertisement

SpringerLink
Log in

Characterization of the Attenuation of Breast Cancer Bone Metastasis in Mice by Zoledronic Acid Using 99mTc bone Scintigraphy

  • Research
  • Published:
Pathology & Oncology Research

Abstract

Metastatic breast cancer often metastasizes to bone. The purposes of the study were (1) to evaluate the use of 99mTc-MDP bone scintigraphy for detection of metastatic bone lesions, and (2) to determine the efficacy of zoledronic acid in mice with breast cancer bone metastasis. All tumor-bearing mice were analyzed with radionuclide bone scintigraphy, X-ray, and histological analysis. The metastatic bone tissue was also harvested and analyzed by western blotting and real-time qPCR. Interestingly, zoledronic acid significantly decreased both the tumor burden and the incidence of bone metastasis in mice. In addition, histomorphometric, stereological, and molecular biology analyses demonstrated that zoledronic acid may function to inhibit breast cancer cell growth in the bone microenvironment and regulate the function of osteoblasts and osteoclasts in tumor-bearing mice. Finally, the attenuation of breast cancer bone metastasis using zoledronic acid can be accurately characterized by 99mTc bone scintigraphy in mice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Chen WQ, Zeng HM, Zheng RS, Zhang SW, He J (2012) Cancer incidence and mortality in China, 2007. Chin J Cancer Res 24:1–8

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Linos E, Spanos D, Rosner BA, Linos K, Hesketh T, Qu JD et al (2008) Effects of reproductive and demographic changes on breast cancer incidence in China: a modeling analysis. J Natl Cancer Inst 100:1352–1360

    Article  PubMed Central  PubMed  Google Scholar 

  3. Lipton A, Uzzo R, Amato RJ, Ellis GK, Hakimian B, Roodman GD et al (2009) The science and practice of bone health in oncology: managing bone loss and metastasis in patients with solid tumors. J Natl Compr Cancer Netw Suppl 7:S1–S29

    CAS  Google Scholar 

  4. Roodman GD (2004) Mechanisms of bone metastasis. N Engl J Med 350:1655–1664

    Article  CAS  PubMed  Google Scholar 

  5. Anderson KC, Alsina M, Bensinger W, Biermann JS, Chanan-Khan A, Cohen AD, et al (2010) NCCN clinical practice guidelines in oncology: multiple myeloma, 2010, v.2. Available at: http://www.24hmb.com/UpLoad/Editor/2010/1/4/2010010471312017.pdf

  6. Luo KW, Ko CH, Yue GG, Lee MY, Siu WS, Lee JK et al (2013) Anti-tumor and anti-osteolysis effects of the metronomic use of zoledronic acid in primary and metastatic breast cancer mouse models. Cancer Lett 339:42–48

    Article  CAS  PubMed  Google Scholar 

  7. Insalaco L, Di Gaudio F, Terrasi M, Amodeo V, Caruso S, Corsini LR et al (2012) Analysis of molecular mechanisms and anti-tumoural effects of zoledronic acid in breast cancer cells. J Cell Mol Med 16:2186–2195

    Article  CAS  PubMed  Google Scholar 

  8. Hiraga T, Williams PJ, Ueda A, Tamura D, Yoneda T (2004) Zoledronic acid inhibits visceral metastases in the 4T1/luc mouse breast cancer model. Clin Cancer Res 10:4559–4567

    Article  CAS  PubMed  Google Scholar 

  9. Jeong J, Lee KS, Choi YK, Oh YJ, Lee HD (2011) Preventive effects of zoledronic acid on bone metastasis in mice injected with human breast cancer cells. J Korean Med Sci 26:1569–1575

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Koto K, Horie N, Kimura S, Murata H, Sakabe T, Matsui T et al (2008) Clinically relevant dose of zoledronic acid inhibits spontaneous lung metastasis in a murine osteosarcoma model. Cancer Lett 274:271–278

    Article  PubMed  Google Scholar 

  11. Rachner TD, Singh SK, Schoppet M, Benad P, Bornhäuser M, Ellenrieder V et al (2010) Zoledronic acid induces apoptosis and changes the TRAIL/OPG ratio in breast cancer cells. Cancer Lett 287:109–116

    Article  CAS  PubMed  Google Scholar 

  12. Hiraga T, Williams PJ, Mundy GR, Yoneda T (2001) The bisphosphonate ibandronate promotes apoptosis in MDA-MB-231 human breast cancer cells in bone metastases. Cancer Res 61:4418–4424

    CAS  PubMed  Google Scholar 

  13. Yoneda T, Willams PJ, Hiraga T, Niewolna M, Nishimura R (2001) A bone-seeking clone exhibits different biological properties from the MDA-MB-231 parental human breast cancer cells and a brain-seeking clone in vivo and in vitro. J Bone Miner Res 16:1486–1495

    Article  CAS  PubMed  Google Scholar 

  14. El-Abdaimi K, Ste-Marie LG, Papavasiliou V, Dion N, Cardinal PE, Huang D et al (2003) Pamidronate prevents the development of skeletal metastasis in nude mice transplanted with human breast cancer cells by reducing tumor burden within bone. Int J Oncol 22:883–890

    CAS  PubMed  Google Scholar 

  15. Even-Sapir E (2005) Imaging of malignant bone involvement by morphologic, scintigraphic, and hybrid modalities. J Nucl Med 46:1356–1367

    PubMed  Google Scholar 

  16. Hamaoka T, Madewell JE, Podoloff DA, Hortobagyi GN, Ueno NT (2004) Bone imaging in metastatic breast cancer. J Clin Oncol 22:2942–2953

    Article  PubMed  Google Scholar 

  17. Padhani A, Husband J (1998) Bone metastases. In: Husband JES, Reznek RH (eds) Imaging in oncology oxford. Isis Medical Media Ltd, U.K., pp 765–787

    Google Scholar 

  18. Yang S, Dong Q, Yao M, Shi M, Ye J, Zhao L et al (2009) Establishment of an experimental human lung adenocarcinoma cell line SPC-A-1BM with high bone metastases potency by 99mTc–MDP bone scintigraphy. Nucl Med Biol 36:313–321

    Article  CAS  PubMed  Google Scholar 

  19. Wu C, Sun Z, Ye Y, Han X, Song X, Liu S (2013) Psoralen inhibits bone metastasis of breast cancer in mice. Fitoterapia 91:205–210

    Article  CAS  PubMed  Google Scholar 

  20. Chen M, Ye Y, Ji G, Liu J (2010) Hesperidin upregulates heme oxygenase–1 to attenuate hydrogen peroxide-induced cell damage in hepatic L02 cells. J Agric Food Chem 58:3330–3335

    Article  CAS  PubMed  Google Scholar 

  21. Mandal MN, Vasireddy V, Jablonski MM, Wang X, Heckenlively JR, Hughes BA et al (2006) Spatial and temporal expression of MFRP and its interaction with CTRP5. Invest Ophthalmol Vis Sci 47:5514–5521

    Article  PubMed  Google Scholar 

  22. Coleman RE, Marshall H, Cameron D, Dodwell D, Burkinshaw R, Keane M et al (2011) Breast-cancer adjuvant therapy with zoledronic acid. N Engl J Med 365:1396–1405

    Article  CAS  PubMed  Google Scholar 

  23. Costa L (2007) Bisphosphonates: reducing the risk of skeletal complications from bone metastasis. Breast 16:S16–S20

    Article  PubMed  Google Scholar 

  24. Gallo M, Luca AD, Lamura L, Normanno N (2012) Zoledronic acid blocks the interaction between mesenchymal stem cells and breast cancer cells: implications for adjuvant therapy of breast cancer. Ann Oncol 23:597–604

    Article  CAS  PubMed  Google Scholar 

  25. Niikura N, Liu J, Hayashi N, Palla S, Tokuda Y, Hortobagyi G et al (2012) Retrospective analysis of antitumor effects of zoledronic acid in breast cancer patients with bone-only metastases. Cancer 118:2039–2047

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Fournier P, Boissier S, Filleur S, Guglielmi J, Cabon F, Colombel M et al (2002) Bisphosphonates inhibit angiogenesis in vitro and testosterone-stimulated vascular regrowth in the ventral prostate in castrated rats. Cancer Res 62:6538–6544

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported by The National Natural Science Foundation of China (No. 30772811, No. 81102597 and No. 81173269), “Shu Guang” project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation (No. 08GG12) and Sponsored by Program of Shanghai Subject Chief Scientist (No. 10XD1404000).

Conflict of Interest

We have no conflict of interest to declare.

Author information

Authors and Affiliations

  1. Department of Breast Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China

    Chunyu Wu, Zhenping Sun & Sheng Liu

  2. Department of Nuclear Medicine, Shanghai Chest Hospital, Shanghai JiaoTong University, Shanghai, 200030, China

    Shunfang Yang

  3. Pharmacology Laboratory of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China

    Xianghui Han, Yiyi Ye & Sheng Liu

  4. Department of Breast Surgery and Pharmacology Laboratory of Traditional Chinese Medicine, Long Hua Hospital, Shanghai University of Traditional Chinese Medicine, 725 South Wanping Road, Shanghai, 200032, China

    Sheng Liu

Authors
  1. Chunyu Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shunfang Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhenping Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xianghui Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yiyi Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sheng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sheng Liu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wu, C., Yang, S., Sun, Z. et al. Characterization of the Attenuation of Breast Cancer Bone Metastasis in Mice by Zoledronic Acid Using 99mTc bone Scintigraphy. Pathol. Oncol. Res. 20, 747–754 (2014). https://doi.org/10.1007/s12253-014-9756-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-014-9756-z

Keywords

Search

Navigation