Materials Transactions Online

Materials Transactions, Vol.57 No.12 (2016) pp.2077-2082
© 2016 The Japan Institute of Metals and Materials

Disruption of Collagen Matrix Alignment in Osteolytic Bone Metastasis Induced by Breast Cancer

Aiko Sekita1, Aira Matsugaki1 and Takayoshi Nakano1

1Division of Materials Science and Engineering, Graduate School of Engineering, Osaka University, Suita 565-0871, Japan

Breast cancer is highly metastatic to bone tissue and causes osteolytic lesions through osteoclast activation. Although the effects of osteolytic metastasis on bone quantity have been well studied, whether osteoclast activation induced by cancer bone metastasis affects the bone microstructure, a notable aspect of the bone quality, remains uncertain. The aim of this study was to clarify the effect of osteolytic bone metastasis in breast cancer on the microstructure of the bone matrix, particularly the integrity of collagen fibril orientation. Osteolytic breast cancer cells induced hyperactivation of osteoclasts both in vivo and in vitro. Osteoclasts differentiated by culture of monocytes in the cancer cell-derived conditioned medium had an increased number of nuclei; more specific podosome structures were organized compared to osteoclasts differentiated in the control medium. These observations suggest that the resorptive capacity of a single osteoclast was abnormally upregulated in the cancer-involving environment, causing geometrically irregular resorption cavities. Histological studies on mouse femurs with metastasis of breast cancer MDA-MB-231 cells revealed that the osteoclasts in the metastatic bone were abnormally large and they generated resorption cavities that are irregular both in size and in shape. Notably, collagen matrix in newly formed bone in metastatic bone exhibited a significantly disorganized architecture. To the best of our knowledge, this is the first report demonstrating that osteolytic bone metastasis induces the disruption of bone matrix alignment, which determines the mechanical function of bone in both intact and diseased bone tissue.


(Received 2016/09/28; Accepted 2016/10/05; Published 2016/11/25)

Keywords: cancer bone metastasis, collagen fibril alignment, osteoclasts, resorption cavity, podosome structure, coupling of bone formation and resorption

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  1. R.E. Coleman: Cancer 80 (1997) 1588-1594.
  2. D.L. Waning and T.A. Guise: Clin. Cancer Res. 20 (2014) 3071-3077.
  3. T. Taube, I. Elomaa, C. Blomqvist, M.N. Beneton and J.A. Kanis: Bone 15 (1994) 161-166.
  4. D.R. Clohisy, D. Palkert, M.L. Ramnaraine, I. Pekurovsky and M.J. Oursler: J. Orthop. Res. 14 (1996) 396-402.
  5. N. Giuliani, S. Colla and V. Rizzoli: Exp. Hematol. 32 (2004) 685-691.
  6. H.K. Vaananen, H. Zhao, M. Mulari and J.M. Halleen: J. Cell Sci. 113 (2000) 377-381.
  7. E. Seeman and P.D. Delmas: N. Engl. J. Med. 354 (2006) 2250-2261.
  8. T. Lin, W. Tong, A. Chandra, S.Y. Hsu, H. Jia, J. Zhu, W.J. Tseng, M.A. Levine, Y. Zhang, S.G. Yan, X.S. Liu, D. Sun, W. Young and L. Qin: Bone Res. 3 (2015) 15028.
  9. N.C. Hunt, Y. Fujikawa, A. Sabokbar, I. Itonaga, A. Harris and N.A. Athanasou: Br. J. Cancer 85 (2001) 78-84.
  10. J.E. Brown, H. Neville-Webbe and R.E. Coleman: Endocr. Relat. Cancer 11 (2004) 207-224.
  11. A.K. Nair, A. Gautieri, S.W. Chang and M.J. Buehler: Nat. Commun. 4 (2013) 1724.
  12. T. Nakano, K. Kaibara, Y. Tabata, N. Nagata, S. Enomoto, E. Marukawa and Y. Umakoshi: Bone 31 (2002) 479-487.
  13. T. Nakano, K. Kaibara, T. Ishimoto, Y. Tabata and Y. Umakoshi: Bone 51 (2012) 741-747.
  14. T. Ishimoto, T. Nakano, Y. Umakoshi, M. Yamamoto and Y. Tabata: J. Bone Miner. Res. 28 (2013) 1170-1179.
  15. A.M. Parfitt: Bone 14 (1993) 435-441.
  16. J.W. Lee, T. Nakano, S. Toyosawa, Y. Tabata and Y. Umakoshi: Mater. Trans. 48 (2007) 337-342.
  17. P. Chavassieux, E. Seeman and P.D. Delmas: Endocr. Rev. 28 (2007) 151-164.
  18. D. Chappard, C. Alexandre, J.C. Laborier, J.M. Robert and G. Riffat: J. Submicrosc. Cytol. 16 (1984) 341-8.
  19. J. Vanderoost, K. Soe, D.M. Merrild, J.M. Delaisse and G.H. van Lenthe: Calcif. Tissue Int. 92 (2013) 240-250.
  20. S.V. Reddy, C. Menaa, F.R. Singer, A. Demulder and G.D. Roodman: J. Bone Miner. Res. 14 Suppl 2 (1999) 3-8.
  21. A. Kukita, C. Chenu, L.M. McManus, G.R. Mundy and G.D. Roodman: J. Clin. Invest. 85 (1990) 1280-1286.
  22. S. Viguet-Carrin, P. Garnero and P.D. Delmas: Osteoporos. Int. 17 (2006) 319-336.
  23. F. Arguello, R.B. Baggs and C.N. Frantz: Cancer Res. 48 (1988) 6876-6881.
  24. Y. Kang, P.M. Siegel, W. Shu, M. Drobnjak, S.M. Kakonen, C. Cordon-Cardo, T.A. Guise and J. Massague: Cancer Cell 3 (2003) 537-549.
  25. I. Boraschi-Diaz and S.V. Komarova: Cytotechnology 68 (2016) 105-114.
  26. S.A. Arkett, S.J. Dixon and S.M. Sims: J. Physiol. 458 (1992) 633-653.
  27. D. Georgess, I. Machuca-Gayet, A. Blangy and P. Jurdic: Cell Adhes. Migr. 8 (2014) 191-204.
  28. K. Piper, A. Boyde and S.J. Jones: Anat. Embryol. (Berl.) 186 (1992) 291-299.
  29. K. Tiedemann, O. Hussein, G. Sadvakassova, Y. Guo, P.M. Siegel and S.V. Komarova: J. Biol. Chem. 284 (2009) 33662-33670.
  30. P. Jurdic, F. Saltel, A. Chabadel and O. Destaing: Eur. J. Cell Biol. 85 (2006) 195-202.
  31. C. Luxenburg, D. Geblinger, E. Klein, K. Anderson, D. Hanein, B. Geiger and L. Addadi: PLoS ONE 2 (2007) e179.
  32. C. Itzstein, F.P. Coxon and M.J. Rogers: Small GTPases 2 (2011) 117-130.
  33. K. Soe and J.M. Delaisse: J. Bone Miner. Res. 25 (2010) 2184-2192.
  34. J. Vanderoost and G.H. van Lenthe: World J. Radiol. 6 (2014) 643-656.
  35. M.E. Abdelgawad, K. Soe, T.L. Andersen, D.M. Merrild, P. Christiansen, P. Kjaersgaard-Andersen and J.M. Delaisse: Bone 67 (2014) 181-188.
  36. A. Matsugaki, Y. Isobe, T. Saku and T. Nakano: J. Biomed. Mater. Res. A 103 (2015) 489-499.


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