Cancer and Metastasis Reviews

, Volume 26, Issue 3–4, pp 705–715 | Cite as

Metastasis: the seed and soil theory gains identity

  • Emmanouil Fokas
  • Rita Engenhart-Cabillic
  • Kiriakos Daniilidis
  • Frank Rose
  • Han-Xiang An
Article

Abstract

The metastatic spread of tumor cells to distant sites represents the major cause of cancer-related deaths. Cancer metastasis involves a series of complex interactions between tumor cells and microenvironment that influence its biological effectiveness and facilitate tumor cell arrest to distant organs. More than a century since Paget developed the theory of seed and soil, the enigma of tissue specificity observed in metastatic colonization of tumor cells begins to unfold itself. The advent of new technologies has led to the discovery of novel molecules and pathways that confer metastasis-associated properties to the cancer cells, mediating organ specificity and unique genetic signatures have been developed using microarray studies. Future clinical studies and new antimetastatic compounds aiming to improve survival of patients with metastasis will most probably be based on these signatures. This review summarizes the plethora of old and new molecules that are strongly correlated with organ-specific metastases and which provide now an identity to the theory of seed and soil.

Keywords

Organ-specific metastasis Colonization Seed and soil Genetic signature 

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References

  1. 1.
    Hanahan, D., & Weinberg, R. A. (2000). The hallmarks of cancer. Cell, 100, 57–0.PubMedCrossRefGoogle Scholar
  2. 2.
    Fidler, I. J. (2002). Critical determinants of metastasis. Seminars Cancer Biology, 12, 89–6.CrossRefGoogle Scholar
  3. 3.
    Fidler, I. J. (2002). The organ microenvironment and cancer metastasis. Differentiation, 70, 498–05.PubMedCrossRefGoogle Scholar
  4. 4.
    Paget, S. (1889). The distribution of secondary growths in cancer of the breast. Lancet, 1, 571–73.CrossRefGoogle Scholar
  5. 5.
    Sugarbaker, D. (1952). Organ selectivity of experimentally induced metastases in rats. Cancer, 5, 606–12.PubMedCrossRefGoogle Scholar
  6. 6.
    Kinsey, D. L. (1960). An experimental study of preferential metastasis. Cancer, 13, 674–76.PubMedCrossRefGoogle Scholar
  7. 7.
    Hart, I. R., & Fidler, I. J. (1980). Role of organ selectivity in the determination of metastatic patterns of B16 melanoma. Cancer Research, 40, 2281–287.PubMedGoogle Scholar
  8. 8.
    Loberg, R. D., Logothetis, C. J., Keller, E. T., & Pienta, K. J. (2005). Pathogenesis and treatment of prostate cancer bone metastases: Targeting the lethal phenotype. Journal of Clinical Oncology, 23, 8232–241.PubMedCrossRefGoogle Scholar
  9. 9.
    Nielsen, O. S., Munro, A. J., & Tannock, I. F. (1991). Bone metastases: Pathophysiology and management policy. Journal of Clinical Oncology, 9, 509–24.PubMedGoogle Scholar
  10. 10.
    Guise, T. A., Mohammad, K. S., Clines, G., Stebbins, E. G., Wong, D. H., Higgins, L. S., et al. (2006). Basic mechanisms responsible for osteolytic and osteoblastic bone metastases. Clinical Cancer Research, 12, 6213s–216s.PubMedCrossRefGoogle Scholar
  11. 11.
    Roodman, G. (2004). Mechanisms of disease. Mechanisms of bone metastasis. New England Journal of Medicine, 350, 1655–664.PubMedCrossRefGoogle Scholar
  12. 12.
    Mundy, G. (2002). Metastasis to the bone: Causes, consequences and therapeutic opportunities. Nature Reviews Cancer, 2, 584–93.PubMedCrossRefGoogle Scholar
  13. 13.
    Logothetis, C. J., & Lin, S. H. (2005). Osteoblasts in prostate cancer metastasis to bone. Nature Reviews Cancer, 5, 21–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Koeneman, K. S., Yeung, F., & Chung, L. W. (1999). Osteomimetic properties of prostate cancer cells: A hypothesis supporting the predilection of prostate cancer metastasis and growth in the bone environment. Prostate, 39, 246–61.PubMedCrossRefGoogle Scholar
  15. 15.
    Mundy, G. R. (2003). Endothelin-1 and osteoblastic metastasis. PNAS, 100, 10588–0589.PubMedCrossRefGoogle Scholar
  16. 16.
    Shioide, M., & Noda, M. (2003). Endothelin modulates osteopontin and osteocalcin messenger ribonucleic acid expression in rat osteoblastic osteosarcoma cells. Journal of Cell Biochemistry, 53, 176–80.CrossRefGoogle Scholar
  17. 17.
    Kozawa, O., Kawamura, H., Hatakeyama, D., Matsuno, H., & Uematsu, T. (2000). Endothelin-1 induces vascular endothelial growth factor synthesis in osteoblasts: Involvement of p38 mitogen-activated protein kinase. Cell Signal, 12, 375–80.PubMedCrossRefGoogle Scholar
  18. 18.
    Nelson, J. B., Hedican, S. P., George, D. J., Reddi, A. H., Piantadosi, S., Eisenberger, M. A., et al. (1995). Identification of endothelin-1 in the pathophysiology of metastatic adenocarcinoma of the prostate. Nature Medicine, 1, 944–49.PubMedCrossRefGoogle Scholar
  19. 19.
    Abe, E. (2006). Function of BMPs and BMP antagonists in adult bone. Annals of New York Academy of Sciences, 1068, 41–3.CrossRefGoogle Scholar
  20. 20.
    Dai, J., Keller, J., Zhang, J., Lu, Y., Yao, Z., & Keller, E. T. (2005). Bone morphogenetic protein-6 promotes osteoblastic prostate cancer bone metastases through a dual mechanism. Cancer Research, 65, 8274–285.PubMedCrossRefGoogle Scholar
  21. 21.
    Asahina, I., Sampath, T. K., & Hauschka, P. V. (1996). Human osteogenic protein-1 induces chondroblastic, osteoblastic, and/or adipocytic differentiation of clonal murine target cells. Experimental Cell Research, 222, 38–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Honda, Y., Knutsen, R., Strong, D. D., Sampath, T. K., Baylink, D. J., & Mohan, S. (1997). Osteogenic protein-1 stimulates mRNA levels of BMP-6 and decreases mRNA levels of BMP-2 and -4 in human osteosarcoma cells. Calcified Tissue International, 60, 297–01.PubMedCrossRefGoogle Scholar
  23. 23.
    Goya, M., Ishii, G., Miyamoto, S., Hasebe, T., Nagai, K., Yonou, H., et al. (2006). Prostate-specific antigen induces apoptosis of osteoclast precursors: Potential role in osteoblastic bone metastases of prostate cancer. Prostate, 66, 1573–584.PubMedCrossRefGoogle Scholar
  24. 24.
    Nadiminty, N., Lou, W., Lee, S. O., Mehraein-Ghomi, F., Kirk, J. S., Conroy, J. M., et al. (2006). Prostate-specific antigen modulates genes involved in bone remodeling and induces osteoblast differentiation of human osteosarcoma cell line SaOS-2. Clinical Cancer Research, 12, 1420–430.PubMedCrossRefGoogle Scholar
  25. 25.
    Clevers, H. (2006). Wt/beta-catenin signaling in development and disease. Cell, 127, 469–80.PubMedCrossRefGoogle Scholar
  26. 26.
    Chen, G., Shukeir, N., Potti, A., Sircar, K., Aprikian, A., Goltzman, D., et al. (2004). Up-regulation of Wnt-1 and β-catenin production in patients with advanced metastatic prostate carcinoma. Cancer, 101, 1345–356.PubMedCrossRefGoogle Scholar
  27. 27.
    Hall, C. L., Bafico, A., Dai, J., Aaronson, S. A., & Keller, E. T. (2005). Prostate cancer cells promote osteoblastic bone metastases through Wnts. Cancer Research, 65, 7554–560.PubMedGoogle Scholar
  28. 28.
    Shariat, S. F., Shalev, M., Menesses-Diaz, A., Kim, I. Y., Kattan, M. W., Wheeler, T. M., et al. (2001). Preoperative plasma levels of transforming growth factor β1 (TGF-β1) strongly predict progression in patients undergoing radical prostatectomy. Journal of Clinical Oncology, 19, 2856–864.PubMedGoogle Scholar
  29. 29.
    Cao, Y., Zhou, Z., de Crombrugghe, B., Nakashima, K., Guan, H., Duan, X., et al. (2005). Osterix, a transcription factor for osteoblast differentiation, mediates antitumor activity in murine osteosarcoma. Cancer Research, 65, 1124–128.PubMedCrossRefGoogle Scholar
  30. 30.
    Nakashima, K., Zhou, X., Kunkel, G., Zhang, Z., Deng, J. M., Behringer, R. R., et al. (2002). The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell, 108, 17–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Pratap, J., Lian, J. B., Javed, A., Barnes, G. L., van Wijnen, A. J., Stein, J. L., et al. (2006). Regulatory roles of Runx2 in metastatic tumor and cancer cell interactions with bone. Cancer and Metastasis Reviews, 25, 589–00.PubMedCrossRefGoogle Scholar
  32. 32.
    Barnes, G. L., Javed, A., Waller, S. M., Kamal, M. H., Hebert, K. E., Hassan, M. Q., et al. (2003). Osteoblast-related transcription factors Runx2 (Cbfa1/AML3) and MSX2 mediate the expression of bone sialoprotein in human metastatic breast cancer cells. Cancer Research, 63, 2631–637.PubMedGoogle Scholar
  33. 33.
    Barnes, G. L., Hebert, K. E., Kamal, M., Javed, A., Einhorn, T. A., Lian, J. B., et al. (2004). Fidelity of Runx2 activity in breast cancer cells is required for the generation of metastases-associated osteolytic disease. Cancer Research, 64, 4506–513.PubMedCrossRefGoogle Scholar
  34. 34.
    Sun, Y. X., Schneider, A., Jung, Y., Wang, J., Dai, J., Wang, J., et al. (2005). Skeletal localization and neutralization of the SDF-1/CXCR4 axis blocks prostate cancer metastasis and growth in osseous sites in vivo. Journal of Bone and Mineral Research, 20, 318–29.PubMedCrossRefGoogle Scholar
  35. 35.
    Vaday, G. G. (2004). CXCR4 and CXCL12 (SDF-1) in prostate cancer: Inhibitory effects of human single chain Fv antibodies. Clinical Cancer Research, 10, 5630–639.PubMedCrossRefGoogle Scholar
  36. 36.
    Blair, J. M., Zhou, H., Seibel, M. J., & Dunstan, C. R. (2006). Mechanisms of disease: Roles of OPG, RANKL and RANK in the pathophysiology of skeletal metastasis. Nature Clinical Practice Oncology, 3, 41–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Dougall, W. C., & Chaisson, M. (2006). The RANK/RANKL/OPG triad in cancer-induced bone diseases. Cancer and Metastasis Reviews, 25, 541–49.PubMedCrossRefGoogle Scholar
  38. 38.
    Liao, J., & McCauley, L. K. (2006). Skeletal metastasis: Established and emerging roles of parathyroid hormone related protein (PTHrP). Cancer and Metastasis Reviews, 25, 559–71.PubMedCrossRefGoogle Scholar
  39. 39.
    Zhang, J., Dai, J., Yao, Z., Lu, Y., Dougall, W., & Keller, E. T. (2003). Soluble receptor activator of nuclear factor kB Fc diminishes prostate cancer progression in bone. Cancer Research, 63, 7883–890.PubMedGoogle Scholar
  40. 40.
    Neville-Webbe, H. L., Cross, N. A., Eaton, C. L., Nyambo, R., Evans, C. A., Coleman, R. E., et al. (2004). Osteoprotegerin (OPG) produced by bone marrow stromal cells protects breast cancer cells from TRAIL-induced apoptosis. Breast Cancer Research and Treatment, 86, 269–79.PubMedCrossRefGoogle Scholar
  41. 41.
    Zhang, J., Dai, J., Qi, Y., Lin, D. L., Smith, P., Strayhorn, C., et al. (2001). Osteoprotegerin inhibits prostate cancer-induced osteoclastogenesis and prevents prostate tumor growth in the bone. Journal of Clinical Investigation, 107, 1235–244.PubMedCrossRefGoogle Scholar
  42. 42.
    Morony, S., Capparelli, C., Sarosi, I., Lacey, D. L., Dunstan, C. R., & Kostenuik, P. J. (2001). Osteoprotegerin inhibits osteolysis and decreases skeletal tumor burden in syngeneic and nude mouse models of experimental bone metastasis. Cancer Research, 61, 4432–436.PubMedGoogle Scholar
  43. 43.
    Moussad, E. E., & Brigstock, D. R. (2002). Connective tissue growth factor: What’s in a name? Molecular Genetics and Metabolism, 71, 276–92.CrossRefGoogle Scholar
  44. 44.
    Morgan, H., Tumber, A., & Hill, P. A. (2004). Breast cancer cells induce osteoclast formation by stimulating host IL-11 production and downregulating granulocyte/macrophage colony-stimulating factor. International Journal of Cancer, 109, 653–60.CrossRefGoogle Scholar
  45. 45.
    de Winter, J. P., ten Dijke, P., de Vries, C. J., van Achterberg, T. A., Sugino, H., de Waele, P., et al. (1996). Follistatins neutralize activin bioactivity by inhibition of activin binding to its type II receptors. Molecular Cell Endocrinology, 116, 105–14.CrossRefGoogle Scholar
  46. 46.
    Leto, G., Incorvaia, L., Badalamenti, G., Tumminello, F. M., Gebbia, N., Flandina, C., et al. (2006). Activin A circulating levels in patients with bone metastasis from breast or prostate cancer. Clinical & Experimental Metastasis, 23, 117–22.CrossRefGoogle Scholar
  47. 47.
    Egeblad, M., & Werb, Z. (2002). New functions for the matrix metalloproteinases in cancer progression. Nature Reviews Cancer, 2, 161–74.PubMedCrossRefGoogle Scholar
  48. 48.
    Liu, Y. J., Xu, Y., & Yu, Q. (2006). Full-length ADAMTS-1 and the ADAMTS-1 fragments display pro- and antimetastatic activity, respectively. Oncogene, 25, 2452–467.PubMedCrossRefGoogle Scholar
  49. 49.
    Yang, Y., Macleod, V., Bendre, M., Huang, Y., Theus, A. M., Miao, H. Q., et al. (2005). Heparanase promotes the spontaneous metastasis of myeloma cells to bone. Blood, 105, 1303–309.PubMedCrossRefGoogle Scholar
  50. 50.
    Kang, S. H., Siegel, P. M., Shu, W., Drobnjak, M., Kakonen, S. M., Cordon-Cardo, C., et al. (2003). A multigenic program mediating breast cancer metastasis to bone. Cancer Cell, 3, 537–49.PubMedCrossRefGoogle Scholar
  51. 51.
    Mukherji, S. K., Armao, D., & Joshi, V. M. (2001). Cervical nodal metastases in squamous cell carcinoma of the head and neck: What to expect. Head and Neck, 23, 995–005.PubMedCrossRefGoogle Scholar
  52. 52.
    O’Donnell, R. K., Kupferman, M., Wei, S. J., Singhal, S., Weber, R., O’Malley, B., et al. (2005). Gene expression signature predicts lymphatic metastasis in squamous cell carcinoma of the oral cavity. Oncogene, 24, 1244–251.PubMedCrossRefGoogle Scholar
  53. 53.
    Greenberg, J. S., Fowler, R., Gomez, J., Mo, V., Roberts, D., El Naggar, A. K., et al. (2004). Extent of extracapsular spread: A critical prognosticator in oral tongue cancer. Cancer, 97, 1464–470.CrossRefGoogle Scholar
  54. 54.
    Zhou, X., Temam, S., Oh, M., Pungpravat, N., Huang, B. L., Mao, L., et al. (2006). Global expression-based classification of lymph node metastasis and extracapsular spread of oral tongue squamous cell carcinoma. Neoplasia, 8, 925–32.PubMedCrossRefGoogle Scholar
  55. 55.
    Roepman, P., Wessels, L. F., Kettelarij, N., Kemmeren, P., Miles, A. J., Lijnzaad, P., et al. (2005). An expression profile for diagnosis of lymph node metastases from primary head and neck squamous cell carcinomas. Nature Genetics, 37, 182–86.PubMedCrossRefGoogle Scholar
  56. 56.
    Roepman, P., Kemmeren, P., Wessels, L. F., Slootweg, P. J., & Holstege, F. C. (2006). Multiple robust signatures for detecting lymph node metastasis in head and neck cancer. Cancer Research, 66, 2361–366.PubMedCrossRefGoogle Scholar
  57. 57.
    Roepman, P., de Jager, A., Groot Koerkamp, M. J., Kummer, J. A., Slootweg, P. J., & Holstege, F. C. (2006). Maintenance of head and neck tumor gene expression profiles upon lymph node metastasis. Cancer Research, 66, 11110–1114.PubMedCrossRefGoogle Scholar
  58. 58.
    Roepman, P., de Koning, E., van Leenen, D., de Weger, R. A., Kummer, J. A., Slootweg, P. J., et al. (2007). Dissection of a metastatic gene expression signature into distinct components. Genome Biology, 7, R117.CrossRefGoogle Scholar
  59. 59.
    Chu, J. H., Sun, Z. Y., Meng, X. L., Wu, J. H., He, G. L., Liu, G. M., et al. (2006). Differential metastasis-associated gene analysis of prostate carcinoma cells derived from primary tumor and spontaneous lymphatic metastasis in nude mice with orthotopic implantation of PC-3M cells. Cancer Letters, 233, 79–8.PubMedCrossRefGoogle Scholar
  60. 60.
    Kikuchi, T., Daigo, Y., Katagiri, T., Tsunoda, T., Okada, K., Kakiuchi, S., et al. (2003). Expression profiles of non-small cell lung cancers on cDNA microarrays: Identification of genes for prediction of lymph-node metastasis and sensitivity to anti-cancer drugs. Oncogene, 22, 2192–205.PubMedCrossRefGoogle Scholar
  61. 61.
    Kobayashi, K., Imai, K., & Nakamura, Y. (2003). Expression profiles of non-small cell lung cancers on DNA microarrays: Identification of genes for prediction of lymph-node metastasis and sensitivity to anti-cancer drugs. Oncogene, 22, 2105–192.CrossRefGoogle Scholar
  62. 62.
    Langer, C. J., & Mehta, M. P. (2005). Current management of brain metastases, with a focus on systemic options. Journal of Clinical Oncology, 23, 6207–219.PubMedCrossRefGoogle Scholar
  63. 63.
    Kim, L. S., Huang, S., Lu, W., Lev, D. C., & Price, J. E. (2004). Vascular endothelial growth factor expression promotes the growth of breast cancer brain metastases in nude mice. Clinical & Experimental Metastasis, 21, 107–18.CrossRefGoogle Scholar
  64. 64.
    Yano, S., Shinohara, H., Herbst, R. S., Kuniyasu, H., Bucana, C. D., Ellis, L. M., et al. (2000). Expression of vascular endothelial growth factor is necessary but not sufficient for production and growth of brain metastasis. Cancer Research, 60, 4959–967.PubMedGoogle Scholar
  65. 65.
    Sierra, A., Price, J., Garcia-Ramirez, M., Mendez, O., Lopez, L., & Fabra, A. (1997). Astrocyte derived cytokines contribute to the metastatic brain specificity of breast cancer cells. Laboratory Investigation, 77, 357–68.PubMedGoogle Scholar
  66. 66.
    Entschladen, F., Drell, T. L., 4th, Lang, K., Joseph, J., & Zaenker, K. S. (2004). Tumour-cell migration, invasion, and metastasis: Navigation by neurotransmitters. Lancet Oncology, 5, 254–58.PubMedCrossRefGoogle Scholar
  67. 67.
    Drell, T. L., 4th, Joseph, J., Lang, K., Niggemann, B., Zaenker, K. S., & Entschladen, F. (2003). Effects of neurotransmitters on the chemokinesis and chemotaxis of MDA-MB-468 human breast carcinoma cells. Breast Cancer Research and Treatment, 80, 63–0.PubMedCrossRefGoogle Scholar
  68. 68.
    Steeg, P. (2003). Metastasis suppressors alter the signal transduction of cancer cells. Nature Reviews Cancer, 3, 55–3.PubMedCrossRefGoogle Scholar
  69. 69.
    Steeg, P. (2004). Perspectives on classic articles: Metastasis suppressor genes. Journal of the National Cancer Institute, 96, E4.PubMedCrossRefGoogle Scholar
  70. 70.
    Stark, A. M., Tongers, K., Maass, N., Mehdorn, H. M., & Held-Feindt, J. (2005). Reduced metastasis-suppressor gene mRNA-expression in breast cancer brain metastases. Journal of Cancer Research and Clinical Oncology, 31, 191.CrossRefGoogle Scholar
  71. 71.
    Fidler, I. J. (1973). Selection of successive tumor lines for metastasis. Nature, 242, 148–49.Google Scholar
  72. 72.
    Fidler, I. J., Gruys, E., Cifone, M. A., Barnes, Z., & Bucana, C. (1981). Demonstration of multiple phenotypic diversity in a murine melanoma of recent origin. Journal of the National Cancer Institute, 67, 947–56.PubMedGoogle Scholar
  73. 73.
    Boukerche, H., Baril, P., Tabone, E., Berard, F., Sanhadji, K., Balme, B., et al. (2000). A new Mr 55,000 surface protein implicated in melanoma progression: Association with a metastatic phenotype. Cancer Research, 60, 5848–856.PubMedGoogle Scholar
  74. 74.
    Huang, S. (2007). Regulation of metastases by signal transducer and activator of transcription 3 signaling pathway: Clinical implications. Cancer Research, 13, 1362–366.CrossRefGoogle Scholar
  75. 75.
    Xie, T. X., Huang, F. J., Aldape, K. D., Kang, S. H., Liu, M., Gershenwald, J. E., et al. (2006). Activation of stat3 in human melanoma promotes brain metastasis. Clinical Cancer Research, 66, 3188–196.Google Scholar
  76. 76.
    Lee, J. H., Miele, M. E., Hicks, D. J., Phillips, K. K., Trent, J. M, Weissman, B. E., et al. (1998). KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. Journal of the National Cancer Institute, 88, 1731–737.CrossRefGoogle Scholar
  77. 77.
    Sarris, M., Scolyer, R. A., Konopka, M., Thompson, J. F., Harper, C. G., & Lee, C. S. (2004). Cytoplasmic expression of nm23 predicts the potential for cerebral metastasis in patients with primary cutaneous melanoma. Melanoma Research, 14, 23–7.PubMedCrossRefGoogle Scholar
  78. 78.
    Denkins, Y., Reiland, J., Roy, M., Sinnappah-Kang, N. D., Galjour, J., Murry, B. P., et al. (2004). Brain metastases in melanoma: Roles of neurotrophins. Neuro-Oncology, 6, 154–65.PubMedCrossRefGoogle Scholar
  79. 79.
    Marchetti, D., McQuillan, D. J., Spohn, W. C., Carson, D. D., & Nicolson, G. L. (1996). Neurotrophin stimulation of human melanoma cell invasion: Selected enhancement of heparanase activity and heparanase degradation of specific heparan sulfate subpopulations. Cancer Research, 56, 2856–863.PubMedGoogle Scholar
  80. 80.
    Marchetti, D., Li, J., & Shen, R. (2000). Astrocytes contribute to the brain-metastatic specificity of melanoma cells by producing heparanase. Cancer Research, 60, 4767–770.PubMedGoogle Scholar
  81. 81.
    Lin, U. N., & Winer, P. E. (2007). Brain metastases: The HER2 paradigm. Clinical Cancer Research, 13, 1648–655.PubMedCrossRefGoogle Scholar
  82. 82.
    Kirsch, D. G., Ledezma, C. J., Mathews, C. S., Bhan, A. K., Ancukiewicz, M., Hochberg, F. H., et al. (2005). Survival after brain metastases from breast cancer in the trastuzumab era. Journal of Clinical Oncology, 23, 2114–116.PubMedCrossRefGoogle Scholar
  83. 83.
    Palmieri, D., Bronder, J. L., Herring, J. M., Yoneda, T., Weil, R. J., Stark, A. M., et al. (2007). Her-2 overexpression increases the metastatic outgrowth of breast cancer cells in the brain. Cancer Research, 67, 4190–198.PubMedCrossRefGoogle Scholar
  84. 84.
    Ohtaki, T., Shintani, Y., Honda, S., Matsumoto, H., Hori, A., Kanehashi, K., et al. (2001). Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature, 411, 613–17.PubMedCrossRefGoogle Scholar
  85. 85.
    Lee, J. H., & Welch, D. R. (1997). Suppression of metastasis in human breast carcinoma MDA-MB-435 cells after transfection with the metastasis suppressor gene, KiSS-1. Cancer Research, 57, 2384–387.PubMedGoogle Scholar
  86. 86.
    Bandyopadhyay, S., Zhan, R., Chaudhuri, A., Watabe, M., Pai, S. K., Hirota, S., et al. (2006). Interaction of KAI1 on tumor cells with DARC on vascular endothelium leads to metastasis suppression. Nature Medicine, 12, 933–38.PubMedCrossRefGoogle Scholar
  87. 87.
    van der Horst, E. H., Degenhardt, Y. Y., Strelow, A., Slavin, A., Chinn, L., Orf, J., et al. (2005). Metastatic properties and genomic amplification of the tyrosine kinase gene ACK1. Proceedings of National Academy of Sciences of the United States of America, 102, 15901–5906.CrossRefGoogle Scholar
  88. 88.
    Goodison, S., Yuan, J., Sloan, D., Kim, R., Li, C., Popescu, N. C., et al. (2005). The RhoGAP protein DLC-1 functions as a metastasis suppressor in breast cancer cells. Cancer Research, 65, 6042–053.PubMedCrossRefGoogle Scholar
  89. 89.
    Zhang, T., Sun, H. C., Xu, Y., Zhang, K. Z., Wang, L., Qin, L. X., et al. (2005). Overexpression of platelet-derived growth factor receptor-α in endothelial cells of hepatocellular carcinoma associated with high metastatic potential. Clinical Cancer Research, 11, 8557–563.PubMedCrossRefGoogle Scholar
  90. 90.
    Brown, D., & Ruoslahti, E. (2004). Metadherin, a cell surface protein in breast tumors that mediates lung metastasis. Cancer Cell, 5, 365–74.PubMedCrossRefGoogle Scholar
  91. 91.
    Khanna, C., Wan, X., Bose, S., Cassaday, R., Olomu, O., Mendoza, A., et al. (2004). The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis. Nature Medicine, 10, 182–86.PubMedCrossRefGoogle Scholar
  92. 92.
    Minn, A. J., Gupta, G. P., Siegel, P. M., Bos, P. D., Shu, W., Giri, D. D., et al. (2005). Genes that mediate breast cancer metastasis to lung. Nature, 436, 518–24.PubMedCrossRefGoogle Scholar
  93. 93.
    Zhang, T., Sun, H. C., Xu, X., Zhang, K. Z., Wang, L., Qin, L. X., et al. (2005). Overexpression of platelet-derived growth factor receptor alpha in endothelial cells of hepatocellular carcinoma associated with high metastatic potential. Clinical Cancer Research, 11, 8557–563.PubMedCrossRefGoogle Scholar
  94. 94.
    Hwang, R. F., Yokoi, K., Bucana, C. D., Tsan, R., Killion, J. J., Evans, D. B., et al. (2003). Inhibition of platelet-derived growth factor receptor phosphorylation by STI571 (Gleevec) reduces growth and metastasis of human pancreatic carcinoma in an orthotopic nude mouse model. Clinical Cancer Research, 15, 6534–544.Google Scholar
  95. 95.
    Lee, J. H., Park, S. R., & Cha, K. O. (2004). KAI1 COOH-terminal interacting tetraspanin (KITENIN), a member of the Tetraspanin family, interacts with KAI1, a tumor metastasis suppressor, and enhances metastasis of cancer. Cancer Research, 64, 4235–243.PubMedCrossRefGoogle Scholar
  96. 96.
    Saha, S., Bardelli, A., Buckhaults, P., Velculescu, V. E., Rago, C., St Croix, B., et al. (2001). A phosphatase associated with metastasis of colorectal cancer. Science, 294, 1343–346.PubMedCrossRefGoogle Scholar
  97. 97.
    Kato, H., Semba, S., Miskad, U. A., Seo, Y., Kasuga, M., & Yokozaki, H. (2004). High expression of PRL-3 promotes cancer cell motility and liver metastasis in human colorectal cancer: A predictive molecular marker of metachronous liver and lung metastases. Clinical Cancer Research, 10, 7318–328.PubMedCrossRefGoogle Scholar
  98. 98.
    Zeng, Q., Dong, J. M., Guo, K., Li, J., Tan, H. X., Koh, V., et al. (2003). PRL-3 and PRL-1 promote cell migration, invasion, and metastasis. Cancer Research, 63, 2716–722.PubMedGoogle Scholar
  99. 99.
    Fiordalisi, J. J., Keller, P. J., & Cox, A. D. (2006). PRL tyrosine phosphatases regulate Rho family GTPases to promote invasion and motility. Cancer Research, 66, 3153–158.PubMedCrossRefGoogle Scholar
  100. 100.
    Li, J., Guo, K., Koh, V. W., Tang, J. P., Gan, B. Q., Shi, H., et al. (2005). Generation of PRL-3- and PRL-1-specific monoclonal antibodies as potential diagnostic markers for cancer metastases. Clinical Cancer Research, 11, 2104–195.Google Scholar
  101. 101.
    Miyamoto, S., Nakamura, M., Shitara, K., Nakamura, K., Ohki, Y., Ishii, G., et al. (2005). Blockade of paracrine supply of insulin-like growth factors using neutralizing antibodies suppresses the liver metastasis of human colorectal cancers. Clinical Cancer Research, 11, 3494–502.PubMedCrossRefGoogle Scholar
  102. 102.
    Kabbinavar, F. F., Schulz, J., McCleod, M., Patel, T., Hamm, J. T., Hecht, J. R., et al. (2005). Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: Results of a randomized phase II trial. Journal of Clinical Oncology, 23, 3697–705.PubMedCrossRefGoogle Scholar
  103. 103.
    Yoo, P. S., Lopez-Soler, R. I., Longo, W. E., & Cha, C. H. (2006). Liver resection for metastatic colorectal cancer in the age of neoadjuvant chemotherapy and bevacizumab. Clinical Colorectal Cancer, 6, 202–07.PubMedCrossRefGoogle Scholar
  104. 104.
    Kindler, H. L., Friberg, G., Singh, D. A., Locker, G., Nattam, S., Kozloff, M., et al. (2005). Phase II trial of bevacizumab plus gemcitabine in patients with advanced pancreatic cancer. Journal of Clinical Oncology, 23, 8033–040.PubMedCrossRefGoogle Scholar
  105. 105.
    Ellis, L. M., Curley, S. A., & Grothey, A. (2005). Surgical resection after downsizing of colorectal liver metastasis in the era of bevacizumab. Journal of Clinical Oncology, 23, 4853–855.PubMedCrossRefGoogle Scholar
  106. 106.
    Yezhelyev, M. V., Koehl, G., Guba, M., Brabletz, T., Jauch, K. W., Ryan, A., et al. (2004). Inhibition of SRC tyrosine kinase as treatment for human pancreatic cancer growing orthotopically in nude mice. Clinical Cancer Research, 10, 8028–036.PubMedCrossRefGoogle Scholar
  107. 107.
    Stephan, S., Datta, K., Wang, E., Li, J., Brekken, R. A., Parangi, S., et al. (2004). Effect of rapamycin alone and in combination with antiangiogenesis therapy in an orthotopic model of human pancreatic cancer. Clinical Cancer Research, 10, 6993–000.PubMedCrossRefGoogle Scholar
  108. 108.
    Yuki, K., Hirohashi, S., Sakamoto, M., Kanai, T., & Shimosato, Y. (1990). Growth and spread of hepatocellular carcinoma. A review of 240 consecutive autopsy cases. Cancer, 66, 2174–179.PubMedCrossRefGoogle Scholar
  109. 109.
    Ye, Q. H., Qin, L. X., Forgues, M., He, P., Kim, J. W., Peng, A. C., et al. (2003). Predicting hepatitis B virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning. Nature Medicine, 4, 416–23.CrossRefGoogle Scholar
  110. 110.
    van ’t Veer, L. J., Dai, H., van de Vijver, M. J., He, Y. D., Hart, A. A., Mao, M., et al. (2002). Gene expression profiling predicts clinical outcome of breast cancer. Nature, 415, 530–36.CrossRefGoogle Scholar
  111. 111.
    Budhu, A., Forgues, M., Ye, Q. H., Jia, H. L., He, P., Zanetti, K. A., et al. (2006). Prediction of venous metastases, recurrence, and prognosis in hepatocellular carcinoma based on a unique immune response signature of the liver microenvironment. Cancer Cell, 10, 99–11.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Emmanouil Fokas
    • 1
  • Rita Engenhart-Cabillic
    • 1
  • Kiriakos Daniilidis
    • 2
  • Frank Rose
    • 1
  • Han-Xiang An
    • 1
  1. 1.Department of Radiotherapy and Radiation Oncology, University Hospital MarburgMedical Faculty of Philipps University MarburgMarburgGermany
  2. 2.Department of Orthopaedic Surgery, University Hospital MarburgMedical Faculty of Philipps University MarburgMarburgGermany

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