Stem Cell Reviews

, Volume 3, Issue 1, pp 18–29 | Cite as

The Wnt Signal Transduction Pathway in Stem Cells and Cancer Cells: Influence on Cellular Invasion

  • Peter Neth
  • Christian Ries
  • Marisa Karow
  • Virginia Egea
  • Matthias Ilmer
  • Marianne Jochum
Article

Abstract

The regulative network conducting adult stem cells in endogenous tissue repair is of prime interest for understanding organ regeneration as well as preventing degenerative and malignant diseases. One major signal transduction pathway which is involved in the control of these (patho)physiological processes is the Wnt pathway. Recent results obtained in our laboratories showed for the first time that canonical Wnt signaling is critically involved in the control of the migration/invasion behaviour of human mesenchymal stem cells (hMSC). In the first part of this review, we describe that the regenerative state is closely linked to the activation of the Wnt pathway. Central hallmarks of activated stem cells are recapitulated in a similar way also in cancer metastasis, where the acquisition of an invasive cancer stem cell phenotype is associated with the induction of Wnt-mediated epithelial to mesenchymal transition (EMT). In the second part, the influence of proinflammatory cytokines such as transforming growth factor (TGF-)β1, interleukin (Il-)1β, and tumor necrosis factor (TNF-)α is discussed with regard to the invasive characteristics of hMSC. In this context, special attention has been paid on the role of matrix metalloproteinases (MMPs), such as MMP-2, MMP-9 and membrane type 1 (MT1)-MMP, as well as on the tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2. Putative cross-talks between different signal transduction pathways that may amplify the invasive capacity of this stem cell population are also discussed. Finally, the consequences towards future drug-mediated therapeutical modifications of Wnt signaling in stem cells and tumor cells are highlighted.

Keywords

Wnt signaling Stem cell Migration and invasion Epithelial to mesenchymal transition (EMT) Cancer stem cell β-catenin Low-density lipoprotein receptor-related protein 5 (LRP5) Matrix metalloproteinase (MMP) Tissue inhibitor of metalloproteinase (TIMP) Cytokine and chemokine 

Notes

Acknowledgements

We would like to thank Prof. Dr. Edwin Fink for critical reading of the manuscript. Relevant research in the laboratories was funded by grants from the Förderprogramm für Forschung und Lehre of the Ludwig-Maximilians-University of Munich (P. Neth), from the Wilhelm Sander-Stiftung (2002.122.1) and by a contract from the German Federal Ministry of Defense (M/SAB1/5/A001) (C. Ries/M. Jochum).

References

  1. 1.
    Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., et al. (1999). Multilineage potential of adult human mesenchymal stem cells. Science, 284(5411), 143–147.PubMedCrossRefGoogle Scholar
  2. 2.
    Jiang, Y., Jahagirdar, B. N., Reinhardt, R. L., Schwartz, R. E., Keene, C. D., Ortiz-Gonzalez, X. R., et al. (2002). Pluripotency of mesenchymal stem cells derived from adult marrow. Nature, 418(6893), 41–49.PubMedCrossRefGoogle Scholar
  3. 3.
    Jiang, Y., Vaessen, B., Lenvik, T., Blackstad, M., Reyes, M., & Verfaillie, C. M. (2002). Multipotent progenitor cells can be isolated from postnatal murine bone marrow, muscle, and brain. Experimental Hematology, 30(8), 896–904.PubMedCrossRefGoogle Scholar
  4. 4.
    Majumdar, M. K., Thiede, M. A., Haynesworth, S. E., Bruder, S. P., & Gerson, S. L. (2000). Human marrow-derived mesenchymal stem cells (MSCs) express hematopoietic cytokines and support long-term hematopoiesis when differentiated toward stromal and osteogenic lineages. Journal of Hematotherapy & Stem Cell Research, 9(6), 841–848.CrossRefGoogle Scholar
  5. 5.
    Cheng, L., Hammond, H., Ye, Z., Zhan, X., & Dravid, G. (2003). Human adult marrow cells support prolonged expansion of human embryonic stem cells in culture. Stem Cells, 21(2), 131–142.PubMedCrossRefGoogle Scholar
  6. 6.
    Aggarwal, S., & Pittenger, M. F. (2005). Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood, 105(4), 1815–1822.PubMedCrossRefGoogle Scholar
  7. 7.
    MacKenzie, T. C., & Flake, A. W. (2001). Human mesenchymal stem cells persist, demonstrate site-specific multipotential differentiation, and are present in sites of wound healing and tissue regeneration after transplantation into fetal sheep. Blood Cells, Molecules & Diseases, 27(3), 601–604.CrossRefGoogle Scholar
  8. 8.
    Kawada, H., Fujita, J., Kinjo, K., Matsuzaki, Y., Tsuma, M., Miyatake, H., et al. (2004). Nonhematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction. Blood, 104(12), 3581–3587.PubMedCrossRefGoogle Scholar
  9. 9.
    Koc, O. N., Gerson, S. L., Cooper, B. W., Dyhouse, S. M., Haynesworth, S. E., Caplan, A. I., et al. (2000). Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy. Journal of Clinical Oncology, 18(2), 307–316.PubMedGoogle Scholar
  10. 10.
    Horwitz, E. M., Prockop, D. J., Fitzpatrick, L. A., Koo, W. W., Gordon, P. L., Neel, M., et al. (1999). Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nature Medicine, 5(3), 309–313.PubMedCrossRefGoogle Scholar
  11. 11.
    Chamberlain, J. R., Schwarze, U., Wang, P. R., Hirata, R. K., Hankenson, K. D., Pace, J. M., et al. (2004). Gene targeting in stem cells from individuals with osteogenesis imperfecta. Science, 303(5661), 1198–1201.PubMedCrossRefGoogle Scholar
  12. 12.
    Prockop, D. J. (2004). Targeting gene therapy for osteogenesis imperfecta. New England Journal of Medicine, 350(22), 2302–2304.PubMedCrossRefGoogle Scholar
  13. 13.
    Khakoo, A. Y., Pati, S., Anderson, S. A., Reid, W., Elshal, M. F., Rovira, I. I., et al. (2006). Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi’s sarcoma. Journal of Experimental Medicine, 203(5), 1235–1247.PubMedCrossRefGoogle Scholar
  14. 14.
    Nakamizo, A., Marini, F., Amano, T., Khan, A., Studeny, M., Gumin, J., et al. (2005). Human bone marrow-derived mesenchymal stem cells in the treatment of gliomas. Cancer Research, 65(8), 3307–3318.PubMedGoogle Scholar
  15. 15.
    Bianco, P., & Robey, P. G. (2001). Stem cells in tissue engineering. Nature, 414(6859), 118–121.PubMedCrossRefGoogle Scholar
  16. 16.
    Meriane, M., Duhamel, S., Lejeune, L., Galipeau, J., & Annabi, B. (2006). Cooperation of matrix metalloproteinases with the RhoA/Rho kinase and mitogen-activated protein kinase kinase-1/extracellular signal-regulated kinase signaling pathways is required for the sphingosine-1-phosphate-induced mobilization of marrow-derived stromal cells. Stem Cells, 24(11), 2557–2565.PubMedCrossRefGoogle Scholar
  17. 17.
    Korbling, M., & Estrov, Z. (2003). Adult stem cells for tissue repair––A new therapeutic concept? New England Journal of Medicine, 349(6), 570–582.PubMedCrossRefGoogle Scholar
  18. 18.
    Li, L., & Xie, T. (2005). Stem cell niche: Structure and function. Annual Review of Cell and Developmental Biology, 21, 605–631.PubMedCrossRefGoogle Scholar
  19. 19.
    Wilson, A., & Trumpp, A. (2006). Bone-marrow haematopoietic-stem-cell niches. Nature Reviews. Immunology, 6(2), 93–106.PubMedCrossRefGoogle Scholar
  20. 20.
    Heissig, B., Hattori, K., Dias, S., Friedrich, M., Ferris, B., Hackett, N. R., et al. (2002). Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell, 109(5), 625–637.PubMedCrossRefGoogle Scholar
  21. 21.
    Lapidot, T., & Petit, I. (2002). Current understanding of stem cell mobilization: The roles of chemokines, proteolytic enzymes, adhesion molecules, cytokines, and stromal cells. Experimental Hematology, 30(9), 973–981.PubMedCrossRefGoogle Scholar
  22. 22.
    Lapidot, T., Dar, A., & Kollet, O. (2005). How do stem cells find their way home? Blood, 106(6), 1901–1910.PubMedCrossRefGoogle Scholar
  23. 23.
    Wynn, R. F., Hart, C. A., Corradi-Perini, C., O’Neill, L., Evans, C. A., Wraith, J. E., et al. (2004). A small proportion of mesenchymal stem cells strongly express functionally active CXCR4 receptor capable of promoting migration to bone marrow. Blood, 104, 2643–2645.PubMedCrossRefGoogle Scholar
  24. 24.
    Sordi, V., Malosio, M. L., Marchesi, F., Mercalli, A., Melzi, R., Giordano, T., et al. (2005). Bone marrow mesenchymal stem cells express a restricted set of functionally active chemokine receptors capable of promoting migration to pancreatic islets. Blood, 106, 419–427.PubMedCrossRefGoogle Scholar
  25. 25.
    Von Luttichau, I., Notohamiprodjo, M., Wechselberger, A., Peters, C., Henger, A., Seliger, C., et al. (2005). Human adult CD34- progenitor cells functionally express the chemokine receptors CCR1, CCR4, CCR7, CXCR5, and CCR10 but not CXCR4. Stem Cells Development, 14(3), 329–336.CrossRefGoogle Scholar
  26. 26.
    Son, B. R., Marquez-Curtis, L. A., Kucia, M., Wysoczynski, M., Turner, A. R., Ratajczak, J., et al. (2006). Migration of bone marrow and cord blood mesenchymal stem cells in vitro is regulated by stromal-derived factor-1-CXCR4 and hepatocyte growth factor-c-met axes and involves matrix metalloproteinases. Stem Cells, 24(5), 1254–1264.PubMedCrossRefGoogle Scholar
  27. 27.
    Reya, T., & Clevers H. (2005). Wnt signalling in stem cells and cancer. Nature, 434(7035), 843–850.PubMedCrossRefGoogle Scholar
  28. 28.
    Moon, R. T., Kohn, A. D., De Ferrari, G. V., & Kaykas, A. (2004). WNT and beta-catenin signalling: Diseases and therapies. Nature Reviews. Genetics, 5(9), 691–701.PubMedCrossRefGoogle Scholar
  29. 29.
    Mikels, A. J., & Nusse, R. (2006). Wnts as ligands: Processing, secretion and reception. Oncogene, 25(57), 7461–7468.PubMedCrossRefGoogle Scholar
  30. 30.
    Nelson, W. J., & Nusse, R. (2004). Convergence of Wnt, beta-catenin, and cadherin pathways. Science, 303(5663), 1483–1487.PubMedCrossRefGoogle Scholar
  31. 31.
    Logan, C. Y., & Nusse, R. (2004). The Wnt signaling pathway in development and disease. Annual Review of Cell and Developmental Biology, 20, 781–810.PubMedCrossRefGoogle Scholar
  32. 32.
    Kimelman, D., & Xu, W. (2006). beta-catenin destruction complex: Insights and questions from a structural perspective. Oncogene, 25(57), 7482–7491.PubMedCrossRefGoogle Scholar
  33. 33.
    Arce, L., Yokoyama, N. N., & Waterman, M. L. (2006). Diversity of LEF/TCF action in development and disease. Oncogene, 25(57), 7492–7504.PubMedCrossRefGoogle Scholar
  34. 34.
    Kawano, Y., & Kypta, R. (2003). Secreted antagonists of the Wnt signalling pathway. Journal of Cell Science, 116(Pt 13), 2627–2634.PubMedCrossRefGoogle Scholar
  35. 35.
    Niehrs, C. (2006). Function and biological roles of the Dickkopf family of Wnt modulators. Oncogene, 25(57), 7469–7481.PubMedCrossRefGoogle Scholar
  36. 36.
    He, X., Semenov, M., Tamai, K., & Zeng, X. (2004). LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling: Arrows point the way. Development, 131(8), 1663–1677.PubMedCrossRefGoogle Scholar
  37. 37.
    Cadigan, K. M., & Nusse, R. (1997). Wnt signaling: A common theme in animal development. Genes & Development, 11(24), 3286–3305.Google Scholar
  38. 38.
    Jamora, C., & Fuchs, E. (2002). Intercellular adhesion, signalling and the cytoskeleton. Nature Cell Biology, 4(4), E101–E108.PubMedCrossRefGoogle Scholar
  39. 39.
    Schambony, A., Kunz, M., & Gradl, D. (2004). Cross-regulation of Wnt signaling and cell adhesion. Differentiation, 72(7), 307–318.PubMedCrossRefGoogle Scholar
  40. 40.
    Brembeck, F. H., Rosario, M., & Birchmeier, W. (2006). Balancing cell adhesion and Wnt signaling, the key role of beta-catenin. Current Opinion in Genetics & Development, 16(1), 51–59.CrossRefGoogle Scholar
  41. 41.
    Beachy, P. A., Karhadkar, S. S., & Berman, D. M. (2004). Tissue repair and stem cell renewal in carcinogenesis. Nature, 432(7015), 324–331.PubMedCrossRefGoogle Scholar
  42. 42.
    Barker, N., & Clevers, H. (2006). Mining the Wnt pathway for cancer therapeutics. Nature Reviews. Drug Discovery, 5(12), 997–1014.PubMedCrossRefGoogle Scholar
  43. 43.
    Pardal, R., Clarke, M. F., & Morrison, S. J. (2003). Applying the principles of stem-cell biology to cancer. Nature Reviews. Cancer, 3(12), 895–902.PubMedCrossRefGoogle Scholar
  44. 44.
    Fukui, T., Kondo, M., Ito, G., Maeda, O., Sato, N., Yoshioka, H., et al. (2005). Transcriptional silencing of secreted frizzled related protein 1 (SFRP 1) by promoter hypermethylation in non-small-cell lung cancer. Oncogene, 24(41), 6323–6327.PubMedCrossRefGoogle Scholar
  45. 45.
    Mazieres, J., He, B., You, L., Xu, Z., Lee, A. Y., Mikami, I., et al. (2004). Wnt inhibitory factor-1 is silenced by promoter hypermethylation in human lung cancer. Cancer Research, 64(14), 4717–4720.PubMedCrossRefGoogle Scholar
  46. 46.
    You, L., Kim, J., He, B., Xu, Z., McCormick, F., & Jablons, D. M. (2006). Wnt-1 signal as a potential cancer therapeutic target. Drug News & Perspectives, 19(1), 27–31.CrossRefGoogle Scholar
  47. 47.
    Kirikoshi, H., Sekihara, H., & Katoh, M. (2001). Up-regulation of Frizzled-7 (FZD7) in human gastric cancer. International Journal of Oncology, 19(1), 111–115.PubMedGoogle Scholar
  48. 48.
    Uematsu, K., He, B., You, L., Xu, Z., McCormick, F., & Jablons, D. M. (2003). Activation of the Wnt pathway in non small cell lung cancer: Evidence of dishevelled overexpression. Oncogene, 22(46), 7218–7221.PubMedCrossRefGoogle Scholar
  49. 49.
    Brabletz, T., Jung, A., Spaderna, S., Hlubek, F., & Kirchner, T. (2005). Opinion: Migrating cancer stem cells—An integrated concept of malignant tumour progression. Nature Reviews. Cancer, 5(9), 744–749.PubMedCrossRefGoogle Scholar
  50. 50.
    Tse, J. C., & Kalluri, R. (2007). Mechanisms of metastasis: Epithelial-to-mesenchymal transition and contribution of tumor microenvironment. Journal of Cellular Biochemistry, in press.Google Scholar
  51. 51.
    Brabletz, T., Jung, A., Reu, S., Porzner, M., Hlubek, F., Kunz-Schughart, L. A., et al. (2001). Variable beta-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment. Proceedings of the National Academy of Sciences of the United States of America, 98(18), 10356–10361.PubMedCrossRefGoogle Scholar
  52. 52.
    Brabletz, T., Hlubek, F., Spaderna, S., Schmalhofer, O., Hiendlmeyer, E., Jung, A., et al. (2005). Invasion and metastasis in colorectal cancer: Epithelial-mesenchymal transition, mesenchymal-epithelial transition, stem cells and beta-catenin. Cells Tissues Organs, 179(1–2), 56–65.PubMedCrossRefGoogle Scholar
  53. 53.
    Gupta, G. P., & Massague, J. (2006). Cancer metastasis: Building a framework. Cell, 127(4), 679–695.PubMedCrossRefGoogle Scholar
  54. 54.
    Korinek, V., Barker, N., Moerer, P., Van Donselaar, E., Huls, G., Peters, P. J., et al. (1998). Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4. Nature Genetics, 19(4), 379–383.PubMedCrossRefGoogle Scholar
  55. 55.
    Willert, K., Brown, J. D., Danenberg, E., Duncan, A. W., Weissman, I. L., Reya, T., et al. (2003). Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature, 423(6938), 448–452.PubMedCrossRefGoogle Scholar
  56. 56.
    Reya, T., Duncan, A. W., Ailles, L., Domen, J., Scherer, D. C., Willert, K., et al. (2003). A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature, 423(6938), 409–414.PubMedCrossRefGoogle Scholar
  57. 57.
    Rattis, F. M., Voermans, C., & Reya, T. (2004). Wnt signaling in the stem cell niche. Current Opinion in Hematology, 11(2), 88–94.PubMedCrossRefGoogle Scholar
  58. 58.
    De Boer, J., Wang, H. J., & Van Blitterswijk, C. (2004). Effects of Wnt signaling on proliferation and differentiation of human mesenchymal stem cells. Tissue Engineering, 10(3–4), 393–401.Google Scholar
  59. 59.
    Boland, G. M., Perkins, G., Hall, D. J., & Tuan, R. S. (2004). Wnt 3a promotes proliferation and suppresses osteogenic differentiation of adult human mesenchymal stem cells. Journal of Cellular Biochemistry, 93(6), 1210–1230.PubMedCrossRefGoogle Scholar
  60. 60.
    Ross, S. E., Hemati, N., Longo, K. A., Bennett, C. N., Lucas, P. C., Erickson, R. L., et al. (2000). Inhibition of adipogenesis by Wnt signaling. Science, 289(5481), 950–953.PubMedCrossRefGoogle Scholar
  61. 61.
    Derfoul, A., Carlberg, L., Tuan, R. S., & Hall, D. J. (2004). Differential regulation of osteogenic marker gene expression by Wnt-3a in embryonic mesenchymal multipotential progenitor cells. Differentiation, 72(5), 209–223.PubMedCrossRefGoogle Scholar
  62. 62.
    Gregory, C. A., Singh, H., Perry, A. S., & Prockop, D. J. (2003). The Wnt signaling inhibitor dickkopf-1 is required for reentry into the cell cycle of human adult stem cells from bone marrow. Journal of Biological Chemistry, 278(30), 28067–28078.PubMedCrossRefGoogle Scholar
  63. 63.
    Neth, P., Ciccarella, M., Egea, V., Hoelters, J., Jochum, M., & Ries, C. (2006). Wnt signaling regulates the invasion capacity of human mesenchymal stem cells. Stem Cells, 24(8), 1892–1903.PubMedCrossRefGoogle Scholar
  64. 64.
    Tetsu, O., & McCormick, F. (1999). Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature, 398(6726), 422–426.PubMedCrossRefGoogle Scholar
  65. 65.
    Liotta, L. A. (1984). Tumor invasion and metastases: Role of the basement membrane. Warner-Lambert Parke-Davis Award lecture. American Journal of Pathology, 117(3), 339–348.PubMedGoogle Scholar
  66. 66.
    Albini, A., Benelli, R., Noonan, D. M., & Brigati, C. (2004). The “chemoinvasion assay”: A tool to study tumor and endothelial cell invasion of basement membranes. International Journal of Developmental Biology, 48(5–6), 563–571.PubMedCrossRefGoogle Scholar
  67. 67.
    Ries, C., Egea, V., Karow, M., Kolb, H., Jochum, M., & Neth, P. (2007). MMP-2, MT1-MMP, and TIMP-2 are essential for the invasive capacity of human mesenchymal stem cells: Differential regulation by inflammatory cytokines. Blood, 109(9), 4055–4063.Google Scholar
  68. 68.
    Klein, P. S., & Melton, D. A. (1996). A molecular mechanism for the effect of lithium on development. Proceedings of the National Academy of Sciences of the United States of America, 93(16), 8455–8459.PubMedCrossRefGoogle Scholar
  69. 69.
    Hedgepeth, C. M., Conrad, L. J., Zhang, J., Huang, H. C., Lee, V. M., & Klein, P. S. (1997). Activation of the Wnt signaling pathway: A molecular mechanism for lithium action. Developmental Biology, 185(1), 82–91.CrossRefGoogle Scholar
  70. 70.
    Qiang, Y. W., Walsh, K., Yao, L., Kedei, N., Blumberg, P. M., Rubin, J. S., et al. (2005). Wnts induce migration/invasion of myeloma plasma cells. Blood, 106, 1786–1793.PubMedCrossRefGoogle Scholar
  71. 71.
    Bienz, M., & Clevers, H. (2000). Linking colorectal cancer to Wnt signaling. Cell, 103(2), 311–320.PubMedCrossRefGoogle Scholar
  72. 72.
    Pollheimer, J., Loregger, T., Sonderegger, S., Saleh, L., Bauer, S., Bilbam, M., et al. (2006). Activation of the canonical wingless/T-cell factor signaling pathway promotes invasive differentiation of human trophoblast. American Journal of Pathology, 168(4), 1134–1147.PubMedCrossRefGoogle Scholar
  73. 73.
    Chisholm, A. D. (2006). Gastrulation: Wnts Signal constriction. Current Biology, 16(20), R874–R876.PubMedCrossRefGoogle Scholar
  74. 74.
    Liebner, S., Cattelino, A., Gallini, R., Rudini, N., Iurlaro, M., Piccolo, S., et al. (2004). Beta-catenin is required for endothelial-mesenchymal transformation during heart cushion development in the mouse. Journal of Cell Biology, 166(3), 359–367.PubMedCrossRefGoogle Scholar
  75. 75.
    Hoelters, J., Ciccarella, M., Drechsel, M., Geissler, C., Gulkan, H., Bocker, W., et al. (2005). Nonviral genetic modification mediates effective transgene expression and functional RNA interference in human mesenchymal stem cells. Journal of Gene Medicine, 7(6), 718–728.PubMedCrossRefGoogle Scholar
  76. 76.
    Verma, U. N., Surabhi, R. M., Schmaltieg, A., Becerra, C., & Gaynor, R. B. (2003). Small interfering RNAs directed against beta-catenin inhibit the in vitro and in vivo growth of colon cancer cells. Clinical Cancer Research, 9(4), 1291–1300.PubMedGoogle Scholar
  77. 77.
    Massague, J. (2004). G1 cell-cycle control and cancer. Nature, 432(7015), 298–306.PubMedCrossRefGoogle Scholar
  78. 78.
    Etheridge, S. L., Spencer, G. J., Heath, D. J., & Genever, P. G. (2004). Expression profiling and functional analysis of wnt signaling mechanisms in mesenchymal stem cells. Stem Cells, 22(5), 849–860.PubMedCrossRefGoogle Scholar
  79. 79.
    Weeraratna, A. T. (2005). A Wnt-er Wonderland—The complexity of Wnt signaling in melanoma. Cancer Metastasis Reviews, 24(2), 237–250.PubMedCrossRefGoogle Scholar
  80. 80.
    Schweizer, L., & Varmus, H. (2003). Wnt/Wingless signaling through beta-catenin requires the function of both LRP/Arrow and frizzled classes of receptors. BMC Cell Biology, 4(1), 4.PubMedCrossRefGoogle Scholar
  81. 81.
    Cong, F., Schweizer, L., & Varmus, H. (2004). Wnt signals across the plasma membrane to activate the beta-catenin pathway by forming oligomers containing its receptors, Frizzled and LRP. Development, 131(20), 5103–5115.PubMedCrossRefGoogle Scholar
  82. 82.
    Kikuchi, A., Yamamoto, H., & Kishida, S. (2006). Multiplicity of the interactions of Wnt proteins and their receptors. Cell Signal, 19(4), 659–671.PubMedCrossRefGoogle Scholar
  83. 83.
    Smalley, M. J., & Dale, T. C. (1999). Wnt signalling in mammalian development and cancer. Cancer Metastasis Reviews, 18(2), 215–230.PubMedCrossRefGoogle Scholar
  84. 84.
    Chen, G., Shukeir, N., Potti, A., Sircar, K., Aprikian, A., Goltzman, D., et al. (2004). Up-regulation of Wnt-1 and beta-catenin production in patients with advanced metastatic prostate carcinoma: Potential pathogenetic and prognostic implications. Cancer, 101(6), 1345–1356.PubMedCrossRefGoogle Scholar
  85. 85.
    Hoang, B. H., Kubo, T., Healey, J. H., Yang, R., Nathan, S. S., Kolb, E. A., et al. (2004). Dickkopf 3 inhibits invasion and motility of Saos-2 osteosarcoma cells by modulating the Wnt-beta-catenin pathway. Cancer Research, 64(8), 2734–2739.PubMedCrossRefGoogle Scholar
  86. 86.
    Hoang, B. H., Kubo, T., Healey, J. H., Sowers, R., Mazza, B., Yang, R., et al. (2004). Expression of LDL receptor-related protein 5 (LRP5) as a novel marker for disease progression in high-grade osteosarcoma. International Journal of Cancer, 109(1), 106–111.CrossRefGoogle Scholar
  87. 87.
    Zi, X., Guo, Y., Simoneau, A. R., Hope, C., Xie, J., Holcombe, R. F., et al. (2005). Expression of Frzb/secreted Frizzled-related protein 3, a secreted Wnt antagonist, in human androgen-independent prostate cancer PC-3 cells suppresses tumor growth and cellular invasiveness. Cancer Research, 65(21), 9762–9770.PubMedCrossRefGoogle Scholar
  88. 88.
    Hiendlmeyer, E., Regus, S., Wassermann, S., Hlubek, F., Haynl, A., Dimmler, A., et al. (2004). Beta-catenin up-regulates the expression of the urokinase plasminogen activator in human colorectal tumors. Cancer Research, 64(4), 1209–1214.PubMedCrossRefGoogle Scholar
  89. 89.
    Mann, B., Gelos, M., Siedow, A., Hanski, M. L., Gretchev, A., Ilyas, M., et al. (1999). Target genes of beta-catenin-T cell-factor/lymphoid-enhancer-factor signaling in human colorectal carcinomas. Proceedings of the National Academy of Sciences of the United States of America, 96(4), 1603–1608.PubMedCrossRefGoogle Scholar
  90. 90.
    Wielenga, V. J., Smits, R., Korinek, V., Smit, L., Kielman, M., Fodde, R., et al. (1999). Expression of CD44 in Apc and Tcf mutant mice implies regulation by the WNT pathway. American Journal of Pathology, 154(2), 515–523.PubMedGoogle Scholar
  91. 91.
    Brabletz, T., Jung, A., Dag, S., Hlubek, F., & Kirchner, T. (1999). Beta-catenin regulates the expression of the matrix metalloproteinase-7 in human colorectal cancer. American Journal of Pathology, 155(4), 1033–1038.PubMedGoogle Scholar
  92. 92.
    Takahashi, M., Tsunoda, T., Seiki, M., Nakamura, Y., & Furukawa, Y. (2002). Identification of membrane-type matrix metalloproteinase-1 as a target of the beta-catenin/Tcf4 complex in human colorectal cancers. Oncogene, 21(38), 5861–5867.PubMedCrossRefGoogle Scholar
  93. 93.
    Nagase, H., & Woessner, J. F., Jr. (1999). Matrix metalloproteinases. Journal of Biological Chemistry, 274(31), 21491–21494.PubMedCrossRefGoogle Scholar
  94. 94.
    Itoh, Y., & Seiki, M. (2006). MT1-MMP: A potent modifier of pericellular microenvironment. Journal of Cellular Physiology, 206(1), 1–8.PubMedCrossRefGoogle Scholar
  95. 95.
    Itoh, Y., Takamura, A., Ito, N., Maru, Y., Sato, H., Suenaga, N., et al. (2001). Homophilic complex formation of MT1-MMP facilitates proMMP-2 activation on the cell surface and promotes tumor cell invasion. EMBO Journal, 20(17), 4782–4793.PubMedCrossRefGoogle Scholar
  96. 96.
    Knauper, V., Will, H., Lopez-Otin, C., Smith, B., Atkinson, S. J., Stanton, H., et al. (1996). Cellular mechanisms for human procolagenase-3 (MMP-13) activation. Evidence that MT1-MMP (MMP-14) and gelatinase a (MMP-2) are able to generate active enzyme. Journal of Biological Chemistry, 271(29), 17124–17131.PubMedCrossRefGoogle Scholar
  97. 97.
    Seiki, M. (2002). The cell surface: The stage for matrix metalloproteinase regulation of migration. Current Opinion in Cell Biology, 14(5), 624–632.PubMedCrossRefGoogle Scholar
  98. 98.
    Bartolome, R. A., Molina-Ortiz, I., Samaniego, R., Sanchez-Mateos, P., Bustelo, X. R., & Teixido, J. (2006). Activation of Vav/Rho GTPase signaling by CXCL12 controls membrane-type matrix metalloproteinase-dependent melanoma cell invasion. Cancer Research, 66(1), 248–258.PubMedCrossRefGoogle Scholar
  99. 99.
    Tam, E. M., Morrison, C. J., Wu, Y. I., Stack, M. S., & Overall, C. M. (2004). Membrane protease proteomics: Isotope-coded affinity tag MS identification of undescribed MT1-matrix metalloproteinase substrates. Proceedings of the National Academy of Sciences of the United States of America, 101(18), 6917–6922.PubMedCrossRefGoogle Scholar
  100. 100.
    Efron, P. A., & Moldawer, L. L. (2004). Cytokines and wound healing: The role of cytokine and anticytokine therapy in the repair response. Journal of Burn Care & Rehabilitation, 25(2), 149–160.CrossRefGoogle Scholar
  101. 101.
    Westermarck, J., & Kahari, V. M. (1999). Regulation of matrix metalloproteinase expression in tumor invasion. FASEB Journal, 13(8), 781–792.PubMedGoogle Scholar
  102. 102.
    Overall, C. M., Wrana, J. L., & Sodek, J. (1991). Transcriptional and post-transcriptional regulation of 72-kDa gelatinase/type IV collagenase by transforming growth factor-beta 1 in human fibroblasts. Comparisons with collagenase and tissue inhibitor of matrix metalloproteinase gene expression. Journal of Biological Chemistry, 266(21), 14064–14071.PubMedGoogle Scholar
  103. 103.
    Ries, C., Kolb, H., & Petrides, P. E. (1994). Regulation of 92-kD gelatinase release in HL-60 leukemia cells: Tumor necrosis factor-alpha as an autocrine stimulus for basal- and phorbol ester-induced secretion. Blood, 83(12), 3638–3646.PubMedGoogle Scholar
  104. 104.
    Ries, C., & Petrides, P. E. (1995). Cytokine regulation of matrix metalloproteinase activity and its regulatory dysfunction in disease. Biological Chemistry Hoppe-Seyler, 376(6), 345–355.PubMedGoogle Scholar
  105. 105.
    Dar, A., Kollet, O., & Lapidot, T. (2006). Mutual, reciprocal SDF-1/CXCR4 interactions between hematopoietic and bone marrow stromal cells regulate human stem cell migration and development in NOD/SCID chimeric mice. Experimental Hematology, 34(8), 967–975.PubMedCrossRefGoogle Scholar
  106. 106.
    Charo, I. F., & Ransohoff, R. M. (2006). The many roles of chemokines and chemokine receptors in inflammation. New England Journal of Medicine, 354(6), 610–621.PubMedCrossRefGoogle Scholar
  107. 107.
    McQuibban, G. A., Butler, G. S., Gong, J. H., Bendall, L., Power, C., Clark-Lewis, I., et al. (2001). Matrix metalloproteinase activity inactivates the CXC chemokine stromal cell-derived factor-1. Journal of Biological Chemistry, 276(47), 43503–43508.PubMedCrossRefGoogle Scholar
  108. 108.
    Itoh, Y., & Seiki, M. (2004). MT1-MMP: An enzyme with multidimensional regulation. Trends in Biochemical Sciences, 29(6), 285–289.PubMedCrossRefGoogle Scholar
  109. 109.
    Jian, H., Shen, X., Liu, I., Semenov, M., He, X., & Wang, X. F. (2006). Smad3-dependent nuclear translocation of beta-catenin is required for TGF-beta1-induced proliferation of bone marrow-derived adult human mesenchymal stem cells. Genes & Development, 20(6), 666–674.CrossRefGoogle Scholar
  110. 110.
    Yu, Q., & Stamenkovic, I. (2000). Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Genes & Development, 14(2), 163–176.Google Scholar
  111. 111.
    Houghton, J., Stoicov, C., Nomura, S., Rogers, A. B., Carlson, J., Li, H., et al. (2004). Gastric cancer originating from bone marrow-derived cells. Science, 306(5701), 1568–1571.PubMedCrossRefGoogle Scholar
  112. 112.
    Sato, N., Meijer, L., Skaltsounis, L., Greengard, P., & Brivanlou, A. H. (2004). Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor. Nature Medicine, 10(1), 55–63.PubMedCrossRefGoogle Scholar
  113. 113.
    Trowbridge, J. J., Xenocostas, A., Moon, R. T., & Bhatia, M. (2006). Glycogen synthase kinase-3 is an in vivo regulator of hematopoietic stem cell repopulation. Nature Medicine, 12(1), 89–98.PubMedCrossRefGoogle Scholar
  114. 114.
    Coussens, L. M., & Werb, Z. (2002). Inflammation and cancer. Nature, 420(6917), 860–867.PubMedCrossRefGoogle Scholar
  115. 115.
    Lepourcelet, M., Chen, Y. N., France, D. S., Wang, H., Crews, P., Peterson, F., et al. (2004). Small-molecule antagonists of the oncogenic Tcf/beta-catenin protein complex. Cancer Cell, 5(1), 91–102.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • Peter Neth
    • 1
    • 2
  • Christian Ries
    • 1
  • Marisa Karow
    • 1
  • Virginia Egea
    • 1
  • Matthias Ilmer
    • 1
  • Marianne Jochum
    • 1
  1. 1.Department of Clinical Chemistry and Clinical BiochemistryLudwig-Maximilians-University of MunichMunichGermany
  2. 2.Abteilung für Klinische Chemie und Klinische BiochemieChirurgische Klinik und Poliklinik – InnenstadtMunichGermany

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