Breast Cancer Research and Treatment

, Volume 101, Issue 2, pp 135–148 | Cite as

Transcriptome analysis reveals an osteoblast-like phenotype for human osteotropic breast cancer cells

  • A. Bellahcène
  • R. Bachelier
  • C. Detry
  • R. Lidereau
  • P. Clézardin
  • V. Castronovo
Preclinical Study

Abstract

Metastatic breast cancer cells exhibit the selective ability to seed and grow in the skeleton. We and others have previously reported that human breast tumors which metastasize to the skeleton overexpress bone matrix extracellular proteins. In an attempt to reveal the osteoblast-like phenotype of osteotropic breast cancer cells, we performed a microarray study on a model of breast cancer bone metastasis consisting of the MDA-MB-231 human cell line and its variant B02 selected for its high capacity to form bone metastases in vivo. Analysis of B02 cells transcriptional profile revealed that 11 and 9 out of the 50 most up- and down-regulated mRNAs, respectively, corresponded to genes which expression has been previously associated with osteoblastic differentiation process. Thus, osteoblast specific cadherin 11 which mediates the differentiation of mesenchymal cells into osteoblastic cells is up-regulated in B02. While S100A4, recently described as a key negative regulator of osteoblast differentiation, is the most down-regulated gene in B02 cells. RT-PCR and western blotting experiments allowed the validation of the modulation of several genes of interest. Using immunohistochemistry, performed on human breast primary tumors and their matched liver and bone metastases, we were able to confirm that the osteoblast-like pattern of gene expression observed in our model holds true in vivo. This is the first report demonstrating a gene-expression pattern corresponding to the acquisition of an osteomimetic phenotype by bone metastatic breast cancer cells.

Keywords

Bone Breast cancer Metastases Osteoblast Osteomimicry 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Notes

Acknowledgements

The authors thank Mrs P. Heneaux, S. Thonard and S. Pierard for expert technical assistance. A. Bellahcène is a Research Associate and C. Detry is a “Télévie” Research Fellow of the National Fund for Scientific Research (NFSR, Belgium). This work was partially supported by grants from the NFSR, the Inter-University Attraction Pole (IAP-P5/31), the University of Liège (Fonds spéciaux), Belgium, l’Association pour la Recherche contre le Cancer (no. 7853) and la Ligue contre le Cancer, France. We acknowledge the support of the European Commission through contract METABRE (CEE LSHC-CT-2004-503049). The authors thank Dr. D. Waltregny and Dr. M.V. Chavez (Metastasis Research Laboratory, University of Liège) for critical reading of the manuscript and all the partners of the METABRE consortium for their participation to fruitful discussions: M. Bracke (Ghent University Hospital, Belgium), R.␣Buccione (Consorzio mario Negri Sud, Italy), P. Clément-Lacroix (Prostrakan, France), S. Eccles (Institute of Cancer Research, UK), A. Sierra (Institut De Recerca Oncologica, Spain), A. Teti (University of l’Aquila, Italy), M. Ugorski (Wroclaw Agriculture University, Poland) and G. van der Pluijm (Leiden University Medical Center, The Netherlands).

Supplementary material

10549_2006_9279_MOESM1_ESM.pdf (376 kb)
Supplementary material

References

  1. 1.
    Bellahcène A, Castronovo V (1995) Increased expression of osteonectin and osteopontin, two bone matrix proteins, in human breast cancer. Am J Pathol 146:95–100PubMedGoogle Scholar
  2. 2.
    Bellahcène A, Merville M-P, Castronovo V (1994) Expression of bone sialoprotein, a bone matrix protein, in human breast cancer. Cancer Res 54:2823–2826PubMedGoogle Scholar
  3. 3.
    Waltregny D, Bellahcène A, Van Riet I, Fisher LW, Young M, Fernandez P, Dewé W, de Leval J, Castronovo V (1998) Prognostic value of bone sialoprotein expression in clinically localized human prostate cancer. J Natl Cancer Inst 90:1000–1008PubMedCrossRefGoogle Scholar
  4. 4.
    Bellahcène A, Kroll M, Liebens F, Castronovo V (1996) Bone sialoprotein detection in human breast cancer cells: a potential predictor of bone metastases. J Bone Min Res 11:665–670Google Scholar
  5. 5.
    Bellahcène A, Menard S, Bufalino R, Moreau L, Castronovo V (1996) Expression of bone sialoprotein in primary human breast cancer is associated with poor survival. Int J Cancer 69:350–353PubMedCrossRefGoogle Scholar
  6. 6.
    Waltregny D, Bellahcène A, de Leval X, Florkin B, Weidle U, Castronovo V (2000) Increased expression of bone sialoprotein in bone metastases compared with visceral metastases in human breast and prostate cancers. J Bone Miner Res 15:834–843PubMedCrossRefGoogle Scholar
  7. 7.
    Koeneman KS, Yeung F, Chung LW (1999) Osteomimetic properties of prostate cancer cells: a hypothesis supporting the predilection of prostate cancer metastasis and growth in the bone environment. Prostate 39:246–261PubMedCrossRefGoogle Scholar
  8. 8.
    Lin DL, Tarnowski CP, Zhang J, Dai J, Rohn E, Patel AH, Morris MD, Keller ET (2001) Bone metastatic LNCaP-derivative C4–2B prostate cancer cell line mineralizes in vitro. Prostate 47:212–221PubMedCrossRefGoogle Scholar
  9. 9.
    Arguello F, Baggs RB, Frantz CN (1988) A murine model of experimental metastasis to bone and bone marrow. Cancer Res 48:6876–6881PubMedGoogle Scholar
  10. 10.
    Sasaki A, Boyce BF, Story B, Wright KR, Chapman M, Boyce R, Mundy GR, Yoneda T (1995) Bisphosphonate risedronate reduces metastatic human breast cancer burden in bone in nude mice. Cancer Res 55:3551–3557PubMedGoogle Scholar
  11. 11.
    Yoneda T, Sasaki A, Mundy GR (1994) Osteolytic bone metastasis in breast cancer. Breast Cancer Res Treat 32:73–84PubMedCrossRefGoogle Scholar
  12. 12.
    Peyruchaud O, Winding B, Pecheur I, Serre CM, Delmas P, Clezardin P (2001) Early detection of bone metastases in a murine model using fluorescent human breast cancer cells: application to the use of the bisphosphonate zoledronic acid in the treatment of osteolytic lesions. J Bone Miner Res 16:2027–2034PubMedCrossRefGoogle Scholar
  13. 13.
    Yoneda T, Williams 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 16:1486–1495PubMedCrossRefGoogle Scholar
  14. 14.
    Kang Y, Siegel PM, Shu W, Drobnjak M, Kakonen SM, Cordon-Cardo C, Guise TA, Massague J (2003) A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 3:537–549PubMedCrossRefGoogle Scholar
  15. 15.
    Pecheur I, Peyruchaud O, Serre CM, Guglielmi J, Voland C, Bourre F, Margue C, Cohen-Solal M, Buffet A, Kieffer N, Clezardin P (2002) Integrin alpha(v)beta3 expression confers on tumor cells a greater propensity to metastasize to bone. Faseb J 16:1266–1268PubMedGoogle Scholar
  16. 16.
    Theilhaber J, Bushnell S, Jackson A, Fuchs R (2001) Bayesian estimation of fold-changes in the analysis of gene expression: the PFOLD algorithm. J Comput Biol 8:585–614PubMedCrossRefGoogle Scholar
  17. 17.
    Bieche I, Parfait B, Le Doussal V, Olivi M, Rio MC, Lidereau R, Vidaud M (2001) Identification of CGA as a novel estrogen receptor-responsive gene in breast cancer: an outstanding candidate marker to predict the response to endocrine therapy. Cancer Res 61:1652–1658PubMedGoogle Scholar
  18. 18.
    de Jong DS, Vaes BL, Dechering KJ, Feijen A, Hendriks JM, Wehrens R, Mummery CL, van Zoelen EJ, Olijve W, Steegenga WT (2004) Identification of novel regulators associated with early-phase osteoblast differentiation. J Bone Miner Res 19:947–958PubMedCrossRefGoogle Scholar
  19. 19.
    Seth A, Lee BK, Qi S, Vary CP (2000) Coordinate expression of novel genes during osteoblast differentiation. J Bone Miner Res 15:1683–1696PubMedCrossRefGoogle Scholar
  20. 20.
    Furushima K, Shimo-Onoda K, Maeda S, Nobukuni T, Ikari K, Koga H, Komiya S, Nakajima T, Harata S, Inoue I (2002) Large-scale screening for candidate genes of ossification of the posterior longitudinal ligament of the spine. J Bone Miner Res 17:128–137PubMedCrossRefGoogle Scholar
  21. 21.
    Beck GR Jr, Zerler B, Moran E (2001) Gene array analysis of osteoblast differentiation. Cell Growth Differ 12:61–83PubMedGoogle Scholar
  22. 22.
    Roman-Roman S, Garcia T, Jackson A, Theilhaber J, Rawadi G, Connolly T, Spinella-Jaegle S, Kawai S, Courtois B, Bushnell S, Auberval M, Call K, Baron R (2003) Identification of genes regulated during osteoblastic differentiation by genome-wide expression analysis of mouse calvaria primary osteoblasts in vitro. Bone 32:474–482PubMedCrossRefGoogle Scholar
  23. 23.
    Marie PJ (2003) Fibroblast growth factor signaling controlling osteoblast differentiation. Gene 316:23–32PubMedCrossRefGoogle Scholar
  24. 24.
    Delany AM, Kalajzic I, Bradshaw AD, Sage EH, Canalis E (2003) Osteonectin-null mutation compromises osteoblast formation, maturation, and survival. Endocrinology 144:2588–2596PubMedCrossRefGoogle Scholar
  25. 25.
    Furlan F, Lecanda F, Screen J, Civitelli R (2001) Proliferation, differentiation and apoptosis in connexin43-null osteoblasts. Cell Commun Adhes 8:367–371PubMedCrossRefGoogle Scholar
  26. 26.
    Lee SW, Tomasetto C, Paul D, Keyomarsi K, Sager R (1992) Transcriptional downregulation of gap-junction proteins blocks junctional communication in human mammary tumor cell lines. J Cell Biol 118:1213–1221PubMedCrossRefGoogle Scholar
  27. 27.
    Wilgenbus KK, Kirkpatrick CJ, Knuechel R, Willecke K, Traub O (1992) Expression of Cx26, Cx32 and Cx43 gap junction proteins in normal and neoplastic human tissues. Int J Cancer 51:522–529PubMedCrossRefGoogle Scholar
  28. 28.
    Kii I, Amizuka N, Shimomura J, Saga Y, Kudo A (2004) Cell–cell interaction mediated by cadherin-11 directly regulates the differentiation of mesenchymal cells into the cells of the osteo-lineage and the chondro-lineage. J Bone Miner Res 19:1840–1849PubMedCrossRefGoogle Scholar
  29. 29.
    Pishvaian MJ, Feltes CM, Thompson P, Bussemakers MJ, Schalken JA, Byers SW (1999) Cadherin-11 is expressed in invasive breast cancer cell lines. Cancer Res 59:947–952PubMedGoogle Scholar
  30. 30.
    Zhang X, Schwarz EM, Young DA, Puzas JE, Rosier RN, O’Keefe RJ (2002) Cyclooxygenase-2 regulates mesenchymal cell differentiation into the osteoblast lineage and is critically involved in bone repair. J Clin Invest 109:1405–1415PubMedCrossRefGoogle Scholar
  31. 31.
    French DM, Kaul RJ, D’Souza AL, Crowley CW, Bao M, Frantz GD, Filvaroff EH, Desnoyers L (2004) WISP-1 is an osteoblastic regulator expressed during skeletal development and fracture repair. Am J Pathol 165:855–867PubMedGoogle Scholar
  32. 32.
    Luo Q, Kang Q, Si W, Jiang W, Park JK, Peng Y, Li X, Luu HH, Luo J, Montag AG, Haydon RC, He TC (2004) Connective tissue growth factor (CTGF) is regulated by Wnt and bone morphogenetic proteins signaling in osteoblast differentiation of mesenchymal stem cells. J Biol Chem 279:55958–55968PubMedCrossRefGoogle Scholar
  33. 33.
    Schutze N, Noth U, Schneidereit J, Hendrich C, Jakob F (2005) Differential expression of CCN-family members in primary human bone marrow-derived mesenchymal stem cells during osteogenic, chondrogenic and adipogenic differentiation. Cell Commun Signal 3:5PubMedCrossRefGoogle Scholar
  34. 34.
    Pereira RC, Durant D, Canalis E (2000) Transcriptional regulation of connective tissue growth factor by cortisol in osteoblasts. Am J Physiol Endocrinol Metab 279:E570–E576PubMedGoogle Scholar
  35. 35.
    Nishida T, Nakanishi T, Asano M, Shimo T, Takigawa M (2000) Effects of CTGF/Hcs24, a hypertrophic chondrocyte-specific gene product, on the proliferation and differentiation of osteoblastic cells in vitro. J Cell Physiol 184:197–206PubMedCrossRefGoogle Scholar
  36. 36.
    Xu J, Smock SL, Safadi FF, Rosenzweig AB, Odgren PR, Marks SC Jr, Owen TA, Popoff SN (2000) Cloning the full-length cDNA for rat connective tissue growth factor: implications for skeletal development. J Cell Biochem 77:103–115PubMedCrossRefGoogle Scholar
  37. 37.
    Ivkovic S, Yoon BS, Popoff SN, Safadi FF, Libuda DE, Stephenson RC, Daluiski A, Lyons KM (2003) Connective tissue growth factor coordinates chondrogenesis and angiogenesis during skeletal development. Development 130:2779–2791PubMedCrossRefGoogle Scholar
  38. 38.
    Lechner A, Schutze N, Siggelkow H, Seufert J, Jakob F (2000) The immediate early gene product hCYR61 localizes to the secretory pathway in human osteoblasts. Bone 27:53–60PubMedCrossRefGoogle Scholar
  39. 39.
    Schutze N, Lechner A, Groll C, Siggelkow H, Hufner M, Kohrle J, Jakob F (1998) The human analog of murine cystein rich protein 61 [correction of 16] is a 1alpha,25-dihydroxyvitamin D3 responsive immediate early gene in human fetal osteoblasts: regulation by cytokines, growth factors, and serum. Endocrinology 139:1761–1770PubMedCrossRefGoogle Scholar
  40. 40.
    Ho NC, Jia L, Driscoll CC, Gutter EM, Francomano CA (2000) A skeletal gene database. J Bone Miner Res 15:2095–2122PubMedCrossRefGoogle Scholar
  41. 41.
    Taguchi Y, Yamamoto M, Yamate T, Lin SC, Mocharla H, DeTogni P, Nakayama N, Boyce BF, Abe E, Manolagas SC (1998) Interleukin-6-type cytokines stimulate mesenchymal progenitor differentiation toward the osteoblastic lineage. Proc Assoc Am Physicians 110:559–574PubMedGoogle Scholar
  42. 42.
    Suga K, Saitoh M, Fukushima S, Takahashi K, Nara H, Yasuda S, Miyata K (2001) Interleukin-11 induces osteoblast differentiation and acts synergistically with bone morphogenetic protein-2 in C3H10T1/2 cells. J Interferon Cytokine Res 21:695–707PubMedCrossRefGoogle Scholar
  43. 43.
    Canalis E, Economides AN, Gazzerro E (2003) Bone morphogenetic proteins, their antagonists, and the skeleton. Endocr Rev 24:218–235PubMedCrossRefGoogle Scholar
  44. 44.
    Abe Y, Abe T, Aida Y, Hara Y, Maeda K (2004) Follistatin restricts bone morphogenetic protein (BMP)-2 action on the differentiation of osteoblasts in fetal rat mandibular cells. J Bone Miner Res 19:1302–1307PubMedCrossRefGoogle Scholar
  45. 45.
    Kortesidis A, Zannettino A, Isenmann S, Shi S, Lapidot T, Gronthos S (2005) Stromal-derived factor-1 promotes the growth, survival, and development of human bone marrow stromal stem cells. Blood 105:3793–3801PubMedCrossRefGoogle Scholar
  46. 46.
    Miles RR, Sluka JP, Halladay DL, Santerre RF, Hale LV, Bloem L, Thirunavukkarasu K, Galvin RJ, Hock JM, Onyia JE (2000) ADAMTS-1: a cellular disintegrin and metalloprotease with thrombospondin motifs is a target for parathyroid hormone in bone. Endocrinology 141:4533–4542PubMedCrossRefGoogle Scholar
  47. 47.
    Kim CH, Park YG, Noh SH, Kim YK (2005) PGE2 induces the gene expression of bone matrix metalloproteinase-1 in mouse osteoblasts by cAMP-PKA signaling pathway. Int J Biochem Cell Biol 37:375–385PubMedCrossRefGoogle Scholar
  48. 48.
    Qin L, Li X, Ko JK, Partridge NC (2005) Parathyroid hormone uses multiple mechanisms to arrest the cell cycle progression of osteoblastic cells from G1 to S phase. J Biol Chem 280:3104–3111PubMedCrossRefGoogle Scholar
  49. 49.
    Duarte WR, Iimura T, Takenaga K, Ohya K, Ishikawa I, Kasugai S (1999) Extracellular role of S100A4 calcium-binding protein in the periodontal ligament. Biochem Biophys Res Commun 255:416–420PubMedCrossRefGoogle Scholar
  50. 50.
    Duarte WR, Shibata T, Takenaga K, Takahashi E, Kubota K, Ohya K, Ishikawa I, Yamauchi M, Kasugai S (2003) S100A4: a novel negative regulator of mineralization and osteoblast differentiation. J Bone Miner Res 18:493–501PubMedCrossRefGoogle Scholar
  51. 51.
    Canfield AE, Sutton AB, Hoyland JA, Schor AM (1996) Association of thrombospondin-1 with osteogenic differentiation of retinal pericytes in vitro. J Cell Sci 109(Pt 2):343–353PubMedGoogle Scholar
  52. 52.
    Zimmerman LB, De Jesus-Escobar JM, Harland RM (1996) The Spemann organizer signal noggin binds and inactivates bone morphogenetic protein 4. Cell 86:599–606PubMedCrossRefGoogle Scholar
  53. 53.
    Aspenberg P, Jeppsson C, Economides AN (2001) The bone morphogenetic proteins antagonist Noggin inhibits membranous ossification. J Bone Miner Res 16:497–500PubMedCrossRefGoogle Scholar
  54. 54.
    Wu XB, Li Y, Schneider A, Yu W, Rajendren G, Iqbal J, Yamamoto M, Alam M, Brunet LJ, Blair HC, Zaidi M, Abe E (2003) Impaired osteoblastic differentiation, reduced bone formation, and severe osteoporosis in noggin-overexpressing mice. J Clin Invest 112:924–934PubMedCrossRefGoogle Scholar
  55. 55.
    Balint E, Lapointe D, Drissi H, van der Meijden C, Young DW, van Wijnen AJ, Stein JL, Stein GS, Lian JB (2003) Phenotype discovery by gene expression profiling: mapping of biological processes linked to BMP-2-mediated osteoblast differentiation. J Cell Biochem 89:401–426PubMedCrossRefGoogle Scholar
  56. 56.
    Garcia T, Roman-Roman S, Jackson A, Theilhaber J, Connolly T, Spinella-Jaegle S, Kawai S, Courtois B, Bushnell S, Auberval M, Call K, Baron R (2002) Behavior of osteoblast, adipocyte, and myoblast markers in genome-wide expression analysis of mouse calvaria primary osteoblasts in vitro. Bone 31:205–211PubMedCrossRefGoogle Scholar
  57. 57.
    Hughes DE, Salter DM, Simpson R (1994) CD44 expression in human bone: a novel marker of osteocytic differentiation. J Bone Miner Res 9:39–44PubMedGoogle Scholar
  58. 58.
    Xiao G, Gopalakrishnan R, Jiang D, Reith E, Benson MD, Franceschi RT (2002) Bone morphogenetic proteins, extracellular matrix, and mitogen-activated protein kinase signaling pathways are required for osteoblast-specific gene expression and differentiation in MC3T3-E1 cells. J Bone Miner Res 17:101–110PubMedCrossRefGoogle Scholar
  59. 59.
    Franceschi RT (1999) The developmental control of osteoblast-specific gene expression: role of specific transcription factors and the extracellular matrix environment. Crit Rev Oral Biol Med 10:40–57PubMedCrossRefGoogle Scholar
  60. 60.
    Franceschi RT, Iyer BS (1992) Relationship between collagen synthesis and expression of the osteoblast phenotype in MC3T3-E1 cells. J Bone Miner Res 7:235–246PubMedCrossRefGoogle Scholar
  61. 61.
    Franceschi RT, Iyer BS, Cui Y (1994) Effects of ascorbic acid on collagen matrix formation and osteoblast differentiation in murine MC3T3-E1 cells. J Bone Miner Res 9:843–854PubMedGoogle Scholar
  62. 62.
    Barnes GL, Javed A, Waller SM, Kamal MH, Hebert KE, Hassan MQ, Bellahcene A, Van Wijnen AJ, Young MF, Lian JB, Stein GS, Gerstenfeld LC (2003) Osteoblast-related transcription factors Runx2 (Cbfa1/AML3) and MSX2 mediate the expression of bone sialoprotein in human metastatic breast cancer cells. Cancer Res 63:2631–2637PubMedGoogle Scholar
  63. 63.
    Yeung F, Law WK, Yeh CH, Westendorf JJ, Zhang Y, Wang R, Kao C, Chung LW (2002) Regulation of human osteocalcin promoter in hormone-independent human prostate cancer cells. J Biol Chem 277:2468–2476PubMedCrossRefGoogle Scholar
  64. 64.
    Yoshida CA, Furuichi T, Fujita T, Fukuyama R, Kanatani N, Kobayashi S, Satake M, Takada K, Komori T (2002) Core-binding factor beta interacts with Runx2 and is required for skeletal development. Nat Genet 32:633–638PubMedCrossRefGoogle Scholar
  65. 65.
    Kundu M, Javed A, Jeon JP, Horner A, Shum L, Eckhaus M, Muenke M, Lian JB, Yang Y, Nuckolls GH, Stein GS, Liu PP (2002) Cbfbeta interacts with Runx2 and has a critical role in bone development. Nat Genet 32:639–644PubMedCrossRefGoogle Scholar
  66. 66.
    Munoz-Sanjuan I, Simandl BK, Fallon JF, Nathans J (1999) Expression of chicken fibroblast growth factor homologous factor (FHF)-1 and of differentially spliced isoforms of FHF-2 during development and involvement of FHF-2 in chicken limb development. Development 126:409–421PubMedGoogle Scholar
  67. 67.
    Noda K, Kuwahara Y (1990) Cytochrome c oxidase activity in preosteoclasts induced by experimental tooth movement. J Electron Microsc (Tokyo) 39:97–100Google Scholar
  68. 68.
    Marrony S, Bassilana F, Seuwen K, Keller H (2003) Bone morphogenetic protein 2 induces placental growth factor in mesenchymal stem cells. Bone 33:426–433PubMedCrossRefGoogle Scholar
  69. 69.
    Castro CH, Stains JP, Sheikh S, Szejnfeld VL, Willecke K, Theis M, Civitelli R (2003) Development of mice with osteoblast-specific connexin43 gene deletion. Cell Commun Adhes 10:445–450PubMedCrossRefGoogle Scholar
  70. 70.
    Hirschi KK, Xu CE, Tsukamoto T, Sager R (1996) Gap junction genes Cx26 and Cx43 individually suppress the cancer phenotype of human mammary carcinoma cells and restore differentiation potential. Cell Growth Differ 7:861–870PubMedGoogle Scholar
  71. 71.
    Lorentzon M, Greenhalgh CJ, Mohan S, Alexander WS, Ohlsson C (2005) Reduced bone mineral density in SOCS-2-deficient mice. Pediatr Res 57:223–226PubMedCrossRefGoogle Scholar
  72. 72.
    von Schroeder HP, Veillette CJ, Payandeh J, Qureshi A, Heersche JN (2003) Endothelin-1 promotes osteoprogenitor proliferation and differentiation in fetal rat calvarial cell cultures. Bone 33:673–684CrossRefGoogle Scholar
  73. 73.
    Gu K, Zhang L, Jin T, Rutherford RB (2004) Identification of potential modifiers of Runx2/Cbfa1 activity in C2C12 cells in response to bone morphogenetic protein-7. Cells Tissues Organs 176:28–40PubMedCrossRefGoogle Scholar
  74. 74.
    Zhou R, Diehl D, Hoeflich A, Lahm H, Wolf E (2003) IGF-binding protein-4: biochemical characteristics and functional consequences. J Endocrinol 178:177–193PubMedCrossRefGoogle Scholar
  75. 75.
    Miyakoshi N, Qin X, Kasukawa Y, Richman C, Srivastava AK, Baylink DJ, Mohan S (2001) Systemic administration of insulin-like growth factor (IGF)-binding protein-4 (IGFBP-4) increases bone formation parameters in mice by increasing IGF bioavailability via an IGFBP-4 protease-dependent mechanism. Endocrinology 142:2641–2648PubMedCrossRefGoogle Scholar
  76. 76.
    Bendre MS, Gaddy-Kurten D, Mon-Foote T, Akel NS, Skinner RA, Nicholas RW, Suva LJ (2002) Expression of interleukin 8 and not parathyroid hormone-related protein by human breast cancer cells correlates with bone metastasis in vivo. Cancer Res 62:5571–5579PubMedGoogle Scholar
  77. 77.
    Chaudhary LR, Spelsberg TC, Riggs BL (1992) Production of various cytokines by normal human osteoblast-like cells in response to interleukin-1 beta and tumor necrosis factor-alpha: lack of regulation by 17 beta-estradiol. Endocrinology 130:2528–2534PubMedCrossRefGoogle Scholar
  78. 78.
    Lehrer S, Diamond EJ, Mamkine B, Stone NN, Stock RG (2004) Serum interleukin-8 is elevated in men with prostate cancer and bone metastases. Technol Cancer Res Treat 3:411PubMedGoogle Scholar
  79. 79.
    Panagakos FS, Kumar S (1995) Differentiation of human osteoblastic cells in culture: modulation of proteases by extracellular matrix and tumor necrosis factor-alpha. Inflammation 19:423–443PubMedCrossRefGoogle Scholar
  80. 80.
    Daci E, Everts V, Torrekens S, Van Herck E, Tigchelaar-Gutterr W, Bouillon R, Carmeliet G (2003) Increased bone formation in mice lacking plasminogen activators. J Bone Miner Res 18:1167–1176PubMedCrossRefGoogle Scholar
  81. 81.
    Borton AJ, Frederick JP, Datto MB, Wang XF, Weinstein RS (2001) The loss of Smad3 results in a lower rate of bone formation and osteopenia through dysregulation of osteoblast differentiation and apoptosis. J Bone Miner Res 16:1754–1764PubMedCrossRefGoogle Scholar
  82. 82.
    Hilton MJ, Gutierrez L, Martinez DA, Wells DE (2005) EXT1 regulates chondrocyte proliferation and differentiation during endochondral bone development. Bone 36:379–386PubMedCrossRefGoogle Scholar
  83. 83.
    Safadi FF, Xu J, Smock SL, Kanaan RA, Selim AH, Odgren PR, Marks SC Jr, Owen TA, Popoff SN (2003) Expression of connective tissue growth factor in bone: its role in osteoblast proliferation and differentiation in vitro and bone formation in vivo. J Cell Physiol 196:51–62PubMedCrossRefGoogle Scholar
  84. 84.
    Miller J, Horner A, Stacy T, Lowrey C, Lian JB, Stein G, Nuckolls GH, Speck NA (2002) The core-binding factor beta subunit is required for bone formation and hematopoietic maturation. Nat Genet 32:645–649PubMedCrossRefGoogle Scholar
  85. 85.
    Bourne S, Polak JM, Hughes SP, Buttery LD (2004) Osteogenic differentiation of mouse embryonic stem cells: differential gene expression analysis by cDNA microarray and purification of osteoblasts by cadherin-11 magnetically activated cell sorting. Tissue Eng 10:796–806PubMedCrossRefGoogle Scholar
  86. 86.
    Kato C, Kojima T, Komaki M, Mimori K, Duarte WR, Takenaga K, Ishikawa I (2004) S100A4 inhibition by RNAi up-regulates osteoblast related genes in periodontal ligament cells. Biochem Biophys Res Commun 326:147–153CrossRefGoogle Scholar
  87. 87.
    Duarte WR, Mikuni-Takagaki Y, Kawase T, Limura T, Oida S, Ohya K, Takenaga K, Ishikawa L, Kasugai S (1999) Effects of mechanical stress on the mRNA expression of S100A4 and cytoskeletal components by periodontal ligament cells. J Med Dent Sci 46:117–122PubMedGoogle Scholar
  88. 88.
    Suzuki H, Nezaki Y, Kuno E, Sugiyama I, Mizutani A, Tsukagoshi N (2003) Functional roles of the tissue inhibitor of metalloproteinase 3 (TIMP-3) during ascorbate-induced differentiation of osteoblastic MC3T3-E1 cells. Biosci Biotechnol Biochem 67:1737–1743PubMedCrossRefGoogle Scholar
  89. 89.
    Ibbotson KJ, Harrod J, Gowen M, D’Souza S, Smith DD, Winkler ME, Derynck R, Mundy GR (1986) Human recombinant transforming growth factor alpha stimulates bone resorption and inhibits formation in vitro. Proc Natl Acad Sci USA 83:2228–2232PubMedCrossRefGoogle Scholar
  90. 90.
    Filanti C, Dickson GR, Di Martino D, Ulivi V, Sanguineti C, Romano P, Palermo C, Manduca P (2000) The expression of metalloproteinase-2, -9, and -14 and of tissue inhibitors-1 and -2 is developmentally modulated during osteogenesis in vitro, the mature osteoblastic phenotype expressing metalloproteinase-14. J Bone Miner Res 15:2154–2168PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2006

Authors and Affiliations

  • A. Bellahcène
    • 1
  • R. Bachelier
    • 2
  • C. Detry
    • 1
  • R. Lidereau
    • 3
  • P. Clézardin
    • 2
  • V. Castronovo
    • 1
  1. 1.Metastasis Research Laboratory, Center of Experimental Cancer ResearchUniversity of LiègeLiègeBelgium
  2. 2.INSERM Unit Research 664LyonFrance
  3. 3.INSERM Unit Research 735/Centre René HugueninSt-CloudFrance

Personalised recommendations