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Tumor Biology

, Volume 34, Issue 3, pp 1391–1397 | Cite as

The effects of Hsp90 expression alteration on spinal metastases of breast carcinoma

  • Wangjun Yan
  • Jianru Xiao
  • Tielong Liu
  • Wending Huang
  • Xinghai Yang
  • Zhipeng Wu
  • Quan Huang
  • Ming Qian
Research Article

Abstract

Previous studies have demonstrated that Hsp90 is closely associated with tumor metastases, and inhibition of Hsp90 expression can result in reduced tumor invasiveness and migration capability. However, its role in spinal metastases of breast carcinoma remains unknown. The paper aimed to further detect Hsp90 expression in a mouse model of spinal metastases of breast carcinoma which was established by left ventricular injection of breast cancer cell lines TM40D to nude mice. The BALB/c nude mice were divided into four groups at random: blank control group (n = 10), model group (n = 30), negative control group (n = 10), and experimental group (n = 30). Mice in the experimental group were given intraperitoneal injection of 12 mg/kg 17-allylamino-demethoxy geldanamycin (17-AAG), an inhibitor for Hsp90. The protein and mRNA expressions of Hsp90 were respectively determined using immunohistochemistry and real-time PCR. Bioluminescence imaging, dissection, and hematoxylin and eosin staining were performed to observe tumor formation and bone damage. Our results suggested that Hsp90 expression in mice with breast cancer metastasis in the spine was significantly higher than that in normal mice. Furthermore, Hsp90 expression was decreased and the spinal metastasis from breast cancer was inhibited by 17-AAG application. Hsp90 could be considered as an indicator to forecast tumor metastasis and provide a target for the treatment of spinal metastasis of breast cancer.

Keywords

Spinal metastases Hsp90 17-Allylamino-demethoxy geldanamycin Breast cancer Real-time PCR 

Notes

Conflicts of interest

The authors declare that they have no competing interests.

References

  1. 1.
    Youlden DR, Cramb SM, Dunn NAM, Muller JM, Pyke CM, Baade PD. The descriptive epidemiology of female breast cancer: an international comparison of screening, incidence, survival and mortality. Cancer Epidemiol. 2012;36(3):237–48.PubMedCrossRefGoogle Scholar
  2. 2.
    Mundy GR. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2002;2(8):584–93.PubMedCrossRefGoogle Scholar
  3. 3.
    Kozlow W, Guise TA. Breast cancer metastasis to bone: mechanisms of osteolysis and implications for therapy. J Mammary Gland Biol Neoplasia. 2005;10(2):169–80.PubMedCrossRefGoogle Scholar
  4. 4.
    Salmon JM, Kilpatrick SE. Pathology of skeletal metastases. Orthop Clin North Am. 2000;31(4):537–44. vii-viii.PubMedCrossRefGoogle Scholar
  5. 5.
    Jolly C, Morimoto RI. Role of the heat shock response and molecular chaperones in oncogenesis and cell death. J Natl Cancer Inst. 2000;92(19):1564–72.PubMedCrossRefGoogle Scholar
  6. 6.
    Stangl K, Gunther C, Frank T, Lorenz M, Meiners S, Ropke T, Stelter L, Moobed M, Baumann G, Kloetzel PM, et al. Inhibition of the ubiquitin–proteasome pathway induces differential heat-shock protein response in cardiomyocytes and renders early cardiac protection. Biochem Biophys Res Commun. 2002;291(3):542–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Fortugno P, Beltrami E, Plescia J, Fontana J, Pradhan D, Marchisio PC, Sessa WC, Altieri DC. Regulation of survivin function by Hsp90. Proc Natl Acad Sci U S A. 2003;100(24):13791.PubMedCrossRefGoogle Scholar
  8. 8.
    Pennati M, Folini M, Zaffaroni N. Targeting survivin in cancer therapy: fulfilled promises and open questions. Carcinogenesis. 2007;28(6):1133–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Webb CP, Hose CD, Koochekpour S, Jeffers M, Oskarsson M, Sausville E, Monks A, Vande Woude GF. The geldanamycins are potent inhibitors of the hepatocyte growth factor/scatter factor-met-urokinase plasminogen activator–plasmin proteolytic network. Cancer Res. 2000;60(2):342–9.PubMedGoogle Scholar
  10. 10.
    Park JW, Yeh MW, Wong MG, Lobo M, Hyun WC, Duh QY, Clark OH. The heat shock protein 90-binding geldanamycin inhibits cancer cell proliferation, down-regulates oncoproteins, and inhibits epidermal growth factor-induced invasion in thyroid cancer cell lines. J Clin Endocrinol Metab. 2003;88(7):3346–53.PubMedCrossRefGoogle Scholar
  11. 11.
    Rutherford SL, Lindquist S. Hsp90 as a capacitor for morphological evolution. Nature. 1998;396(6709):336–42.PubMedCrossRefGoogle Scholar
  12. 12.
    Kato A, Ushio Y, Hayakawa T, Yamada K, Ikeda H, Mogami H. Circulatory disturbance of the spinal cord with epidural neoplasm in rats. J Neurosurg. 1985;63(2):260–5.PubMedCrossRefGoogle Scholar
  13. 13.
    Takahashi M, Ogawa J, Kinoshita Y, Takakura M, Mochizuki K, Satomi K. Experimental study of paraplegia caused by spinal tumors: an animal model of spinal tumors created by transplantation of VX2 carcinoma. Spine J. 2004;4(6):675–80.PubMedCrossRefGoogle Scholar
  14. 14.
    Amundson E, Pradilla G, Brastianos P, Bagley C, Riley 3rd LH, Garonzik IM, McCarthy E, Wolinsky JP, Gokaslan ZL. A novel intravertebral tumor model in rabbits. Neurosurgery. 2005;57(2):341–6. discussion 341–346.PubMedCrossRefGoogle Scholar
  15. 15.
    Arguello F, Baggs RB, Frantz CN. A murine model of experimental metastasis to bone and bone marrow. Cancer Res. 1988;48(23):6876–81.PubMedGoogle Scholar
  16. 16.
    Arguello F, Furlanetto RW, Baggs RB, Graves BT, Harwell SE, Cohen HJ, Frantz CN. Incidence and distribution of experimental metastases in mutant mice with defective organ microenvironments (genotypes Sl/Sld and W/Wv). Cancer Res. 1992;52(8):2304–9.PubMedGoogle Scholar
  17. 17.
    Gibert B, Eckel B, Gonin V, Goldschneider D, Fombonne J, Deux B, Mehlen P, Arrigo A, Clézardin P, Diaz-Latoud C. Targeting heat shock protein 27 (HspB1) interferes with bone metastasis and tumour formation in vivo. Br J Cancer. 2012;107:63–70.PubMedCrossRefGoogle Scholar
  18. 18.
    Zhao Z, Cheng CF, Kim R, Chen M, Woodley D, Li W: Targeting secreted heat shock protein-90alpha (Hsp90α) to prevent breast cancer progression. In: 2010: BioMed Central Ltd; 2010: O14.Google Scholar
  19. 19.
    Sims JD, McCready J, Jay DG. Extracellular heat shock protein (Hsp) 70 and Hsp90α assist in matrix metalloproteinase-2 activation and breast cancer cell migration and invasion. PLoS One. 2011;6(4):e18848.PubMedCrossRefGoogle Scholar
  20. 20.
    Isaacs JS, Xu W, Neckers L. Heat shock protein 90 as a molecular target for cancer therapeutics. Cancer Cell. 2003;3(3):213–7.PubMedCrossRefGoogle Scholar
  21. 21.
    Neckers L. Heat shock protein 90: the cancer chaperone. J Biosci. 2007;32(3):517–30.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Wangjun Yan
    • 1
  • Jianru Xiao
    • 1
  • Tielong Liu
    • 1
  • Wending Huang
    • 1
  • Xinghai Yang
    • 1
  • Zhipeng Wu
    • 1
  • Quan Huang
    • 1
  • Ming Qian
    • 1
  1. 1.Spine Tumor Center, Department of OrthopedicsChangzheng Hospital Affiliated the Second Military Medical UniversityShanghaiChina

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