Therapeutic strategies to target TGF-β in the treatment of bone metastases

Current Pharmaceutical Biotechnology

Volumn 12, Issue 12, 2011, Pages 2121-2137

  Buijs, Jeroen T ^a   Juárez, Patricia ^a   Guise, Theresa A ^a  

^a INDIANA UNIVERSITY   (United States)

Author keywords

Antibodies; Antisense oligonucleotides; Bone metastasis; Breast cancer; EMT; Prostate cancer; Small molecule inhibitors; TGF

Indexed keywords

1 D 11; 2 (5 CHLORO 2 FLUOROPHENYL) 4 (4 PYRIDINYLAMINO)PTERIDINE; 2 G 7; 4 [4 (1,3 BENZODIOXOL 5 YL) 5 (2 PYRIDINYL) 1H IMIDAZOL 2 YL]BENZAMIDE; A 83 01; ANTINEOPLASTIC AGENT; ANTISENSE OLIGONUCLEOTIDE; AP 11014; DISITERTIDE; FRESOLIMUMAB; GW 788388; IN 1130; KI 26894; LERDELIMUMAB; LY 2109761; LY 2157299; LY 364947; LY 550410; LY 580276; METELIMUMAB; PAMIDRONIC ACID; PF 03446062; PF 03446962; SB 505124; SD 093; SM 16; SM 305; TRABEDERSEN; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA INHIBITOR; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ABSENCE OF SIDE EFFECTS; ADVANCED CANCER; ANGIOGENESIS; ARTICLE; ASTROCYTOMA; BONE METASTASIS; BREAST CANCER; CANCER INHIBITION; CANCER STEM CELL; CLINICAL PRACTICE; COLORECTAL CANCER; COLORECTAL CARCINOMA; EPITHELIAL MESENCHYMAL TRANSITION; FOCAL GLOMERULOSCLEROSIS; GLIOBLASTOMA; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; LUNG FIBROSIS; LUNG NON SMALL CELL CANCER; MELANOMA; MOLECULARLY TARGETED THERAPY; NATURAL KILLER CELL; NONHUMAN; OSSIFICATION; OSTEOBLAST; OSTEOCLAST; OSTEOLYSIS; PANCREAS ADENOCARCINOMA; PANCREAS CARCINOMA; PROGNOSIS; PROSTATE CANCER; PROTEIN EXPRESSION; PROTEIN STRUCTURE; RECURRENT CANCER; SCLERODERMA; SIGNAL TRANSDUCTION; T LYMPHOCYTE;

ANIMALS; ANTINEOPLASTIC AGENTS; BONE NEOPLASMS; HUMANS; NEOPLASM METASTASIS; TRANSFORMING GROWTH FACTOR BETA;

EID: 84855235898     PISSN: 13892010     EISSN: 18734316     Source Type: Journal    
DOI: 10.2174/138920111798808293     Document Type: Article

References (196)

1. Coleman, R.E. Skeletal complications of malignancy. Cancer, 1997, 80(8 Suppl), 1588 1594.
2. Jemal, A.; Siegel, R.; Xu, J.; Ward, E. Cancer statistics, 2010. CA Cancer J. Clin., 2010, 60(5), 277-300.
3. Mundy, G.R. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat. Rev. Cancer, 2002, 2(8), 584-593.
4. Roodman, G.D. Mechanisms of bone metastasis. N. Engl. J. Med., 2004, 350(16), 1655-1664.
5. Korpal, M.; Yan, J.; Lu, X.; Xu, S.; Lerit, D.A.; Kang, Y. Imaging transforming growth factor-beta signaling dynamics and therapeutic response in breast cancer bone metastasis. Nat. Med., 2009, 15(8), 960-966.
6. Kang, Y.; Siegel, P.M.; Shu, W.; Drobnjak, M.; Kakonen, S.M.; Cordon-Cardo, C.; Guise, T.A.; Massague, J. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell, 2003, 3(6), 537-549.
7. Guise, T.A. Breaking down bone: new insight into site-specific mechanisms of breast cancer osteolysis mediated by metalloproteinases. Genes. Dev., 2009, 23(18), 2117-2123.
8. Yingling, J.M.; Blanchard, K.L.; Sawyer, J.S. Development of TGF-beta signalling inhibitors for cancer therapy. Nat. Rev. Drug Discov., 2004, 3(12), 1011-1022.
9. Massague, J.; Blain, S.W.; Lo, R.S. TGFbeta signaling in growth control, cancer, and heritable disorders. Cell, 2000, 103(2), 295-309.
10. ten Dijke, P.; Arthur, H.M. Extracellular control of TGFbeta signalling in vascular development and disease. Nat. Rev. Mol. Cell Biol., 2007, 8(11), 857-869.
11. Blobe, G.C.; Schiemann, W.P.; Lodish, H.F. Role of transforming growth factor beta in human disease. N. Engl. J. Med., 2000, 342(18), 1350-1358.
12. Massague, J. How cells read TGF-beta signals. Nat. Rev. Mol. Cell Biol., 2000, 1(3), 169-178.
13. Feng, X.H.; Derynck, R. Specificity and versatility in tgf-beta signaling through Smads. Annu. Rev. Cell Dev. Biol., 2005, 21, 659-693.
14. Derynck, R.; Zhang, Y.E. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature, 2003, 425(6958), 577-584.
15. Wu, M.Y.; Hill, C.S. Tgf-beta superfamily signaling in embryonic development and homeostasis. Dev. Cell, 2009, 16(3), 329-343.
16. Daly, A.C.; Randall, R.A.; Hill, C.S. Transforming growth factor beta-induced Smad1/5 phosphorylation in epithelial cells is mediated by novel receptor complexes and is essential for anchorage-independent growth. Mol. Cell Biol., 2008, 28(22), 6889-6902.
17. Liu, I.M.; Schilling, S.H.; Knouse, K.A.; Choy, L.; Derynck, R.; Wang, X.F. TGFbeta-stimulated Smad1/5 phosphorylation requires the ALK5 L45 loop and mediates the pro-migratory TGFbeta switch. EMBO J., 2009, 28(2), 88-98.
18. Pardali, E.; Goumans, M.J.; Ten Dijke, P. Signaling by members of the TGF-beta family in vascular morphogenesis and disease. Trends Cell Biol., 2010, 20(9), 556-567.
19. Siegel, P.M.; Shu, W.; Massague, J. Mad upregulation and Id2 repression accompany transforming growth factor (TGF)-betamediated epithelial cell growth suppression. J. Biol. Chem., 2003, 278(37), 35444-35450.
20. Seyedin, S.M.; Thomas, T.C.; Thompson, A.Y.; Rosen, D.M.; Piez, K.A. Purification and characterization of two cartilage-inducing factors from bovine demineralized bone. Proc. Natl. Acad. Sci. USA, 1985, 82(8), 2267-2271.
21. Seyedin, S.M.; Thompson, A.Y.; Bentz, H.; Rosen, D.M.; McPherson, J.M.; Conti, A.; Siegel, N.R.; Galluppi, G.R.; Piez, K.A. Cartilage-inducing factor-A. Apparent identity to transforming growth factor-beta. J. Biol. Chem., 1986, 261(13), 5693-5695.
22. Janssens, K.; ten Dijke, P.; Janssens, S.; Van Hul, W. Transforming growth factor-beta1 to the bone. Endocr. Rev., 2005, 26(6), 743- 774.
23. Iqbal, J.; Sun, L.; Zaidi, M. Coupling bone degradation to formation. Nat. Med., 2009, 15(7), 729-731.
24. Tang, Y.; Wu, X.; Lei, W.; Pang, L.; Wan, C.; Shi, Z.; Zhao, L.; Nagy, T.R.; Peng, X.; Hu, J.; Feng, X.; Van Hul, W.; Wan, M.; Cao, X. TGF-beta1-induced migration of bone mesenchymal stem cells couples bone resorption with formation. Nat. Med., 2009, 15(7), 757-765.
25. Wu, X.; Pang, L.; Lei, W.; Lu, W.; Li, J.; Li, Z.; Frassica, F.J.; Chen, X.; Wan, M.; Cao, X. Inhibition of sca-1-positive skeletal stem cell recruitment by alendronate blunts the anabolic effects of parathyroid hormone on bone remodeling. Cell Stem Cell, 2010, 7(5),571-580.
26. Canalis, E. Growth factor control of bone mass. J. Cell Biochem., 2009, 108(4), 769-777.
27. Alliston, T.; Choy, L.; Ducy, P.; Karsenty, G.; Derynck, R. TGFbeta- induced repression of CBFA1 by Smad3 decreases cbfa1 and osteocalcin expression and inhibits osteoblast differentiation. EMBO J., 2001, 20(9), 2254-2272.
28. Maeda, S.; Hayashi, M.; Komiya, S.; Imamura, T.; Miyazono, K. Endogenous TGF-beta signaling suppresses maturation of osteoblastic mesenchymal cells. EMBO J., 2004, 23(3), 552-563.
29. Karsdal, M.A.; Andersen, T.A.; Bonewald, L.; Christiansen, C. Matrix metalloproteinases (MMPs) safeguard osteoblasts from apoptosis during transdifferentiation into osteocytes: MT1-MMP maintains osteocyte viability. DNA Cell Biol., 2004, 23(3), 155-165.
30. Quinn, J.M.; Itoh, K.; Udagawa, N.; Hausler, K.; Yasuda, H.; Shima, N.; Mizuno, A.; Higashio, K.; Takahashi, N.; Suda, T.; Martin, T.J.; Gillespie, M.T. Transforming growth factor beta affects osteoclast differentiation via direct and indirect actions. J. Bone Miner Res., 2001, 16(10), 1787-1794.
31. Sells Galvin, R.J.; Gatlin, C.L.; Horn, J.W.; Fuson, T.R. TGF-beta enhances osteoclast differentiation in hematopoietic cell cultures stimulated with RANKL and M-CSF. Biochem. Biophys. Res. Commun., 1999, 265(1), 233-239.
32. Balooch, G.; Balooch, M.; Nalla, R.K.; Schilling, S.; Filvaroff, E.H.; Marshall, G.W.; Marshall, S.J.; Ritchie, R.O.; Derynck, R.; Alliston, T. TGF-beta regulates the mechanical properties and composition of bone matrix. Proc. Natl. Acad. Sci. USA, 2005, 102(52), 18813-18818.
33. Erlebacher, A.; Derynck, R. Increased expression of TGF-beta 2 in osteoblasts results in an osteoporosis-like phenotype. J. Cell Biol., 1996, 132(1-2), 195-210.
34. Mohammad, K.S.; Chen, C.G.; Balooch, G.; Stebbins, E.; McKenna, C.R.; Davis, H.; Niewolna, M.; Peng, X.H.; Nguyen, D.H.; Ionova-Martin, S.S.; Bracey, J.W.; Hogue, W.R.; Wong, D.H.; Ritchie, R.O.; Suva, L.J.; Derynck, R.; Guise, T.A.; Alliston, T. Pharmacologic inhibition of the TGF-beta type I receptor kinase has anabolic and anti-catabolic effects on bone. PLoS ONE, 2009, 4(4), e5275.
35. Edwards, J.R.; Nyman, J.S.; Lwin, S.T.; Moore, M.M.; Esparza, J.; O'Quinn, E.C.; Hart, A.J.; Biswas, S.; Patil, C.A.; Lonning, S.; Mahadevan-Jansen, A.; Mundy, G.R. Inhibition of TGF-beta signaling by 1D11 antibody treatment increases bone mass and quality in vivo. J. Bone Miner Res., 2010, 25(11),2419-2426
36. Derynck, R.; Akhurst, R.J. Differentiation plasticity regulated by TGF-beta family proteins in development and disease. Nat. Cell Biol., 2007, 9(9), 1000-1004.
37. Massague, J.; Chen, Y.G. Controlling TGF-beta signaling. Genes Dev., 2000, 14(6), 627-644.
38. Calonge, M.J.; Massague, J. Smad4/DPC4 silencing and hyperactive Ras jointly disrupt transforming growth factor-beta antiproliferative responses in colon cancer cells. J. Biol. Chem., 1999, 274(47), 33637-33643.
39. Akhurst, R.J.; Derynck, R. TGF-beta signaling in cancer--a doubleedged sword. Trends Cell Biol., 2001, 11(11), S44-51.
40. Massague, J. TGFbeta in Cancer. Cell, 2008, 134(2), 215-230.
41. Pardali, K.; Moustakas, A. Actions of TGF-beta as tumor suppressor and pro-metastatic factor in human cancer. Biochim. Biophys. Acta, 2007, 1775(1), 21-62.
42. Siegel, P.M.; Massague, J. Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer. Nat. Rev. Cancer, 2003, 3(11), 807-821.
43. Tan, A.R.; Alexe, G.; Reiss, M. Transforming growth factor-beta signaling: emerging stem cell target in metastatic breast cancer? Breast Cancer Res. Treat, 2009, 115(3), 453-495.
44. Padua, D.; Massague, J. Roles of TGFbeta in metastasis. Cell Res., 2008, 19, 89-102
45. Folkman, J. Angiogenesis: an organizing principle for drug discovery? Nat. Rev. Drug Discov., 2007, 6(4), 273-286.
46. Hagedorn, H.G.; Bachmeier, B.E.; Nerlich, A.G. Synthesis and degradation of basement membranes and extracellular matrix and their regulation by TGF-beta in invasive carcinomas (Review). Int. J. Oncol., 2001, 18(4), 669-681.
47. Goumans, M.J.; Valdimarsdottir, G.; Itoh, S.; Lebrin, F.; Larsson, J.; Mummery, C.; Karlsson, S.; ten Dijke, P. Activin receptor-like kinase (ALK)1 is an antagonistic mediator of lateral TGFbeta/ALK5 signaling. Mol. Cell, 2003, 12(4), 817-828.
48. Goumans, M.J.; Valdimarsdottir, G.; Itoh, S.; Rosendahl, A.; Sideras, P.; ten Dijke, P. Balancing the activation state of the endothelium via two distinct TGF-beta type I receptors. EMBO J., 2002, 21(7), 1743-1753.
49. Pertovaara, L.; Kaipainen, A.; Mustonen, T.; Orpana, A.; Ferrara, N.; Saksela, O.; Alitalo, K. Vascular endothelial growth factor is induced in response to transforming growth factor-beta in fibroblastic and epithelial cells. J. Biol. Chem., 1994, 269(9), 6271- 6274.
50. de Jong, J.S.; van Diest, P.J.; van der Valk, P.; Baak, J.P. Expression of growth factors, growth-inhibiting factors, and their receptors in invasive breast cancer. II: Correlations with proliferation and angiogenesis. J. Pathol., 1998, 184(1), 53-57.
51. Hasegawa, Y.; Takanashi, S.; Kanehira, Y.; Tsushima, T.; Imai, T.; Okumura, K. Transforming growth factor-beta1 level correlates with angiogenesis, tumor progression, and prognosis in patients with nonsmall cell lung carcinoma. Cancer, 2001, 91(5), 964-971.
52. Tuxhorn, J.A.; McAlhany, S.J.; Yang, F.; Dang, T.D.; Rowley, D.R. Inhibition of transforming growth factor-beta activity decreases angiogenesis in a human prostate cancer-reactive stroma xenograft model. Cancer Res., 2002, 62(21), 6021-6025.
53. Watabe, T.; Nishihara, A.; Mishima, K.; Yamashita, J.; Shimizu, K.; Miyazawa, K.; Nishikawa, S.; Miyazono, K. TGF-beta receptor kinase inhibitor enhances growth and integrity of embryonic stem cell-derived endothelial cells. J. Cell Biol., 2003, 163(6), 1303-1311.
54. Liu, Z.; Kobayashi, K.; van Dinther, M.; van Heiningen, S.H.; Valdimarsdottir, G.; van Laar, T.; Scharpfenecker, M.; Lowik, C.W.; Goumans, M.J.; Ten Dijke, P.; Pardali, E. VEGF and inhibitors of TGFbeta type-I receptor kinase synergistically promote blood-vessel formation by inducing alpha5-integrin expression. J. Cell Sci., 2009, 122(Pt 18), 3294-3302.
55. Thomas, D.A.; Massague, J. TGF-beta directly targets cytotoxic T cell functions during tumor evasion of immune surveillance. Cancer Cell, 2005, 8(5), 369-380.
56. Brabletz, T.; Pfeuffer, I.; Schorr, E.; Siebelt, F.; Wirth, T.; Serfling, E. Transforming growth factor beta and cyclosporin A inhibit the inducible activity of the interleukin-2 gene in T cells through a noncanonical octamer-binding site. Mol. Cell Biol., 1993, 13(2), 1155-1162.
57. Sillett, H.K.; Cruickshank, S.M.; Southgate, J.; Trejdosiewicz, L.K. Transforming growth factor-beta promotes 'death by neglect' in post-activated human T cells. Immunology, 2001, 102(3), 310-316.
58. Gorelik, L.; Flavell, R.A. Transforming growth factor-beta in Tcell biology. Nat. Rev. Immunol., 2002, 2(1), 46-53.
59. Gorelik, L.; Flavell, R.A. Immune-mediated eradication of tumors through the blockade of transforming growth factor-beta signaling in T cells. Nat. Med., 2001, 7(10), 1118-1122.
60. Kalluri, R.; Weinberg, R.A. The basics of epithelial-mesenchymal transition. J. Clin. Invest., 2009, 119(6), 1420-1428.
61. Thiery, J.P.; Acloque, H.; Huang, R.Y.; Nieto, M.A. Epithelialmesenchymal transitions in development and disease. Cell, 2009, 139(5), 871-890.
62. Huber, M.A.; Kraut, N.; Beug, H. Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr. Opin. Cell Biol., 2005, 17(5), 548-558.
63. Batlle, E.; Sancho, E.; Franci, C.; Dominguez, D.; Monfar, M.; Baulida, J.; Garcia De Herreros, A. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat. Cell. Biol., 2000, 2(2), 84-89.
64. Cano, A.; Perez-Moreno, M.A.; Rodrigo, I.; Locascio, A.; Blanco, M.J.; del Barrio, M.G.; Portillo, F.; Nieto, M.A. The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat. Cell. Biol., 2000, 2(2), 76-83.
65. Grunert, S.; Jechlinger, M.; Beug, H. Diverse cellular and molecular mechanisms contribute to epithelial plasticity and metastasis. Nat. Rev. Mol. Cell Biol., 2003, 4(8), 657-665.
66. Al-Hajj, M.; Wicha, M.S.; Benito-Hernandez, A.; Morrison, S.J.; Clarke, M.F. Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. USA, 2003, 100(7), 3983-3988.
67. Collins, A.T.; Berry, P.A.; Hyde, C.; Stower, M.J.; Maitland, N.J. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res, 2005, 65(23), 10946-10951.
68. O'Brien, C.A.; Pollett, A.; Gallinger, S.; Dick, J.E. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature, 2007, 445(7123), 106-110.
69. Reya, T.; Morrison, S.J.; Clarke, M.F.; Weissman, I.L. Stem cells, cancer, and cancer stem cells. Nature, 2001, 414(6859), 105-111.
70. Ricci-Vitiani, L.; Lombardi, D.G.; Pilozzi, E.; Biffoni, M.; Todaro, M.; Peschle, C.; De Maria, R. Identification and expansion of human colon-cancer-initiating cells. Nature, 2007, 445(7123), 111-115.
71. Singh, S.K.; Hawkins, C.; Clarke, I.D.; Squire, J.A.; Bayani, J.; Hide, T.; Henkelman, R.M.; Cusimano, M.D.; Dirks, P.B. Identification of human brain tumour initiating cells. Nature, 2004, 432(7015), 396-401.
72. van den Hoogen, C.; van der Horst, G.; Cheung, H.; Buijs, J.T.; Lippitt, J.M.; Guzman-Ramirez, N.; Hamdy, F.C.; Eaton, C.L.; Thalmann, G.N.; Cecchini, M.G.; Pelger, R.C.; van der Pluijm, G. High aldehyde dehydrogenase activity identifies tumor-initiating and metastasis-initiating cells in human prostate cancer. Cancer Res., 2010, 70(12), 5163-5173.
73. Shipitsin, M.; Campbell, L.L.; Argani, P.; Weremowicz, S.; Bloushtain-Qimron, N.; Yao, J.; Nikolskaya, T.; Serebryiskaya, T.; Beroukhim, R.; Hu, M.; Halushka, M.K.; Sukumar, S.; Parker, L.M.; Anderson, K.S.; Harris, L.N.; Garber, J.E.; Richardson, A.L.; Schnitt, S.J.; Nikolsky, Y.; Gelman, R.S.; Polyak, K. Molecular definition of breast tumor heterogeneity. Cancer Cell, 2007, 11(3), 259-273.
74. Mani, S.A.; Guo, W.; Liao, M.J.; Eaton, E.N.; Ayyanan, A.; Zhou, A.Y.; Brooks, M.; Reinhard, F.; Zhang, C.C.; Shipitsin, M.; Campbell, L.L.; Polyak, K.; Brisken, C.; Yang, J.; Weinberg, R.A. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell, 2008, 133(4), 704-715.
75. Buijs, J.T.; van der Pluijm, G. Osteotropic cancers: from primary tumor to bone. Cancer Lett., 2009, 273(2), 177-193.
76. Yin, J.J.; Selander, K.; Chirgwin, J.M.; Dallas, M.; Grubbs, B.G.; Wieser, R.; Massague, J.; Mundy, G.R.; Guise, T.A. TGF-beta signaling blockade inhibits PTHrP secretion by breast cancer cells and bone metastases development. J. Clin. Invest, 1999, 103(2), 197-206.
77. Kakonen, S.M.; Selander, K.S.; Chirgwin, J.M.; Yin, J.J.; Burns, S.; Rankin, W.A.; Grubbs, B.G.; Dallas, M.; Cui, Y.; Guise, T.A. Transforming growth factor-beta stimulates parathyroid hormonerelated protein and osteolytic metastases via Smad and mitogenactivated protein kinase signaling pathways. J. Biol. Chem., 2002, 277(27), 24571-24578.
78. Deckers, M.; van Dinther, M.; Buijs, J.; Que, I.; Lowik, C.; van der Pluijm, G.; ten Dijke, P. The tumor suppressor Smad4 is required for transforming growth factor beta-induced epithelial to mesenchymal transition and bone metastasis of breast cancer cells. Cancer Res., 2006, 66(4), 2202-2209.
79. Kang, Y.; He, W.; Tulley, S.; Gupta, G.P.; Serganova, I.; Chen, C.R.; Manova-Todorova, K.; Blasberg, R.; Gerald, W.L.; Massague, J. Breast cancer bone metastasis mediated by the Smad tumor suppressor pathway. Proc. Natl. Acad. Sci. USA, 2005, 102(39), 13909-13914.
80. Javelaud, D.; Mohammad, K.S.; McKenna, C.R.; Fournier, P.; Luciani, F.; Niewolna, M.; Andre, J.; Delmas, V.; Larue, L.; Guise, T.A.; Mauviel, A. Stable overexpression of Smad7 in human melanoma cells impairs bone metastasis. Cancer Res., 2007, 67(5), 2317-2324.
81. Dunn, L.K.; Mohammad, K.S.; Fournier, P.G.; McKenna, C.R.; Davis, H.W.; Niewolna, M.; Peng, X.H.; Chirgwin, J.M.; Guise, T.A. Hypoxia and TGF beta drive breast cancer bone metastases through parallel signaling pathways in tumor cells and the bone microenvironment. PLoS ONE, 2009, 4(9), e6896.
82. Kang, Y.; Massague, J. Epithelial-mesenchymal transitions: twist in development and metastasis. Cell, 2004, 118(3), 277-279.
83. Buijs, J.T.; Henriquez, N.V.; van Overveld, P.G.; van der Horst, G.; ten Dijke, P.; van der Pluijm, G. TGF-beta and BMP7 interactions in tumour progression and bone metastasis. Clin. Exp. Metastasis, 2007, 24(8), 609-617.
84. Serganova, I.; Moroz, E.; Vider, J.; Gogiberidze, G.; Moroz, M.; Pillarsetty, N.; Doubrovin, M.; Minn, A.; Thaler, H.T.; Massague, J.; Gelovani, J.; Blasberg, R. Multimodality imaging of TGFbeta signaling in breast cancer metastases. FASEB J., 2009, 23(8), 2662- 2672.
85. Bellahcene, A.; Castronovo, V.; Ogbureke, K.U.; Fisher, L.W.; Fedarko, N.S. Small integrin-binding ligand N-linked glycoproteins (SIBLINGs): multifunctional proteins in cancer. Nat. Rev. Cancer, 2008, 8(3), 212-226.
86. Bellahcene, A.; Kroll, M.; Liebens, F.; Castronovo, V. Bone sialoprotein expression in primary human breast cancer is associated with bone metastases development. J. Bone Miner. Res., 1996, 11(5), 665-670.
87. Hotte, S.J.; Winquist, E.W.; Stitt, L.; Wilson, S.M.; Chambers, A.F. Plasma osteopontin: associations with survival and metastasis to bone in men with hormone-refractory prostate carcinoma. Cancer, 2002, 95(3), 506-512.
88. Zhang, L.; Hou, X.; Lu, S.; Rao, H.; Hou, J.; Luo, R.; Huang, H.; Zhao, H.; Jian, H.; Chen, Z.; Liao, M.; Wang, X. Predictive significance of bone sialoprotein and osteopontin for bone metastases in resected Chinese non-small-cell lung cancer patients: a large cohort retrospective study. Lung Cancer, 2010, 67(1), 114-119.
89. Brown, J.M.; Wilson, W.R. Exploiting tumour hypoxia in cancer treatment. Nat. Rev. Cancer, 2004, 4(6), 437-447.
90. Hiraga, T.; Kizaka-Kondoh, S.; Hirota, K.; Hiraoka, M.; Yoneda, T. Hypoxia and hypoxia-inducible factor-1 expression enhance osteolytic bone metastases of breast cancer. Cancer Res., 2007, 67(9), 4157-4163.
91. McMahon, S.; Charbonneau, M.; Grandmont, S.; Richard, D.E.; Dubois, C.M. Transforming growth factor beta1 induces hypoxiainducible factor-1 stabilization through selective inhibition of PHD2 expression. J. Biol. Chem., 2006, 281(34), 24171-24181.
92. Kelly, R.J.; Morris, J.C. Transforming growth factor-beta: a target for cancer therapy. J. Immunotoxicol., 2010, 7(1), 15-26.
93. Korpal, M.; Kang, Y. Targeting the transforming growth factorbeta signalling pathway in metastatic cancer. Eur. J. Cancer, 2010, 46(7), 1232-1240.
94. Muraoka, R.S.; Dumont, N.; Ritter, C.A.; Dugger, T.C.; Brantley, D.M.; Chen, J.; Easterly, E.; Roebuck, L.R.; Ryan, S.; Gotwals, P.J.; Koteliansky, V.; Arteaga, C.L. Blockade of TGF-beta inhibits mammary tumor cell viability, migration, and metastases. J. Clin.Invest., 2002, 109(12), 1551-1559.
95. Muraoka-Cook, R.S.; Kurokawa, H.; Koh, Y.; Forbes, J.T.; Roebuck, L.R.; Barcellos-Hoff, M.H.; Moody, S.E.; Chodosh, L.A.; Arteaga, C.L. Conditional overexpression of active transforming growth factor beta1 in vivo accelerates metastases of transgenic mammary tumors. Cancer Res., 2004, 64(24), 9002-9011.
96. Siegel, P.M.; Shu, W.; Cardiff, R.D.; Muller, W.J.; Massague, J. Transforming growth factor beta signaling impairs Neu-induced mammary tumorigenesis while promoting pulmonary metastasis.Proc. Natl. Acad. Sci. USA, 2003, 100(14), 8430-8435.
97. Arteaga, C.L.; Carty-Dugger, T.; Moses, H.L.; Hurd, S.D.; Pietenpol, J.A. Transforming growth factor beta 1 can induce estrogen-independent tumorigenicity of human breast cancer cells in athymic mice. Cell Growth Differ., 1993, 4(3), 193-201.
98. Arteaga, C.L.; Hurd, S.D.; Winnier, A.R.; Johnson, M.D.; Fendly, B.M.; Forbes, J.T. Anti-transforming growth factor (TGF)-beta antibodies inhibit breast cancer cell tumorigenicity and increase mouse spleen natural killer cell activity. Implications for a possible role of tumor cell/host TGF-beta interactions in human breast cancer progression. J. Clin. Invest., 1993, 92(6), 2569-2576.
99. Nam, J.S.; Suchar, A.M.; Kang, M.J.; Stuelten, C.H.; Tang, B.; Michalowska, A.M.; Fisher, L.W.; Fedarko, N.S.; Jain, A.; Pinkas, J.; Lonning, S.; Wakefield, L.M. Bone sialoprotein mediates the tumor cell-targeted prometastatic activity of transforming growth factor beta in a mouse model of breast cancer. Cancer Res., 2006, 66(12), 6327-6335.
100. Nam, J.S.; Terabe, M.; Kang, M.J.; Chae, H.; Voong, N.; Yang, Y.A.; Laurence, A.; Michalowska, A.; Mamura, M.; Lonning, S.; Berzofsky, J.A.; Wakefield, L.M. Transforming growth factor beta subverts the immune system into directly promoting tumor growth through interleukin-17. Cancer Res., 2008, 68(10), 3915-3923.
101. Nam, J.S.; Terabe, M.; Mamura, M.; Kang, M.J.; Chae, H.; Stuelten, C.; Kohn, E.; Tang, B.; Sabzevari, H.; Anver, M.R.; Lawrence, S.; Danielpour, D.; Lonning, S.; Berzofsky, J.A.; Wakefield, L.M. An anti-transforming growth factor beta antibody suppresses metastasis via cooperative effects on multiple cell compartments. Cancer Res., 2008, 68(10), 3835-3843.
102. Biswas, S.; Wilburn, C.; Munoz, S.A.; Sterling, J.A.; Lonning, S.; Mundy, G.R. Monoclonal Antibody to Transforming Growth Factor b Inhibits Tumor Burden and Osteolysis in a Pre-clinical Model of Bone Metastasis. J. Bone Miner. Res., 2008, 23(SA187).
103. Mead, A.L.; Wong, T.T.; Cordeiro, M.F.; Anderson, I.K.; Khaw, P.T. Evaluation of anti-TGF-beta2 antibody as a new postoperative anti-scarring agent in glaucoma surgery. Invest. Ophthalmol. Vis. Sci., 2003, 44(8), 3394-3401.
104. Thompson, J.E.; Vaughan, T.J.; Williams, A.J.; Wilton, J.; Johnson, K.S.; Bacon, L.; Green, J.A.; Field, R.; Ruddock, S.; Martins, M.; Pope, A.R.; Tempest, P.R.; Jackson, R.H. A fully human antibody neutralising biologically active human TGFbeta2 for use in therapy. J. Immunol. Methods, 1999, 227(1-2), 17-29.
105. Cordeiro, M.F.; Gay, J.A.; Khaw, P.T. Human anti-transforming growth factor-beta2 antibody: a new glaucoma anti-scarring agent. Invest. Ophthalmol. Vis. Sci., 1999, 40(10), 2225-2234.
106. National library of Medicine (US). Safety Study of GC1008 in Patients With Focal Segmental Glomerulosclerosis (FSGS) of Single Doses of GC1008 in Patients With Treatment Resistant Idiopathic FSGS 2007. http://clinicaltrials.gov/show/NCT00464321 (Accessed Feb 7, 2011).
107. National library of Medicine (US). Safety and Efficacy Study of GC1008 to Treat Renal Cell Carcinoma or Malignant Melanoma 2006. http://clinicaltrials.gov/show/NCT00356460 (Accessed Feb 7, 2011).
108. National library of Medicine (US). Effects of Monoclonal Antibody GC1008 in Blood Samples From Patients With Unresectable Locally Advanced or Metastatic Kidney Cancer or Malignant Melanoma Treated on Clinical Trial NCI-06-C-0200 2008. http://clinicaltrials.gov/show/NCT00899444 (Accessed Feb 7, 2011).
109. Morris, J.C.; Shapiro, G.I.; Tan, A.R.; Lawrence, D.P.; Olencki, T.E.; Dezube, B.J.; J., H.F.; M., R.; A., B.J. Phase I/II Study of GC1008: A human anti-transforming growth factor-beta (TGF-β) monoclonal antibody (MAb) in patients with advanced malignant melanoma (MM) or renal cell carcinoma (RCC). J. Clin. Oncol., 2008, 26(Suppl), 9028.
110. National library of Medicine (US). Study of GC1008 in Patients With Idiopathic Pulmonary Fibrosis (IPF) 2005. http://clinicaltrials.gov/show/NCT00125385 (Accessed Feb 7, 2011).
111. Mancuso, P.; Shalinsky, D.R.; Calleri, A.; Quarna, J.; Antoniotti, P.; Jilani, I.; Hu-Lowe, D.; Jiang, X.; Gallo-Stampino, C.; Bertolini, F. Evaluation of ALK-1 expression in circulating endothelial cells (CECs) as an exploratory biomarker for PF-03446962 undergoing phase I trial in cancer patients. J. Clin.Oncol., 2009, 27:15s, abstr 3573.
112. National library of Medicine (US). A First In Patient, Study Of Investigational Drug PF-03446962 In Patients With Advanced Solid Tumors 2007. http://clinicaltrials.gov/show/NCT00557856 (Accessed Feb 7, 2011).
113. Yang, Y.A.; Dukhanina, O.; Tang, B.; Mamura, M.; Letterio, J.J.; MacGregor, J.; Patel, S.C.; Khozin, S.; Liu, Z.Y.; Green, J.; Anver, M.R.; Merlino, G.; Wakefield, L.M. Lifetime exposure to a soluble TGF-beta antagonist protects mice against metastasis without adverse side effects. J. Clin. Invest., 2002, 109(12), 1607-1615.
114. Bandyopadhyay, A.; Zhu, Y.; Cibull, M.L.; Bao, L.; Chen, C.; Sun, L. A soluble transforming growth factor beta type III receptor suppresses tumorigenicity and metastasis of human breast cancer MDA-MB-231 cells. Cancer Res., 1999, 59(19), 5041-5046.
115. Bandyopadhyay, A.; Lopez-Casillas, F.; Malik, S.N.; Montiel, J.L.; Mendoza, V.; Yang, J.; Sun, L.Z. Antitumor activity of a recombinant soluble betaglycan in human breast cancer xenograft. Cancer Res., 2002, 62(16), 4690-4695.
116. Serrati, S.; Margheri, F.; Pucci, M.; Cantelmo, A.R.; Cammarota, R.; Dotor, J.; Borras-Cuesta, F.; Fibbi, G.; Albini, A.; Del Rosso, M. TGFbeta1 antagonistic peptides inhibit TGFbeta1-dependent angiogenesis. Biochem. Pharmacol., 2009, 77(5), 813-825.
117. National library of Medicine (US). Efficacy and Safety Study of p144 to Treat Skin Fibrosis in Systemic Sclerosis 2007. http://clinicaltrials.gov/show/NCT00574613 (Accessed Feb 7, 2011).
118. Bennett, C.F.; Swayze, E.E. RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform. Annu. Rev. Pharmacol. Toxicol., 2010, 50, 259-293.
119. Crooke, S.T. Progress in antisense technology. Annu. Rev. Med., 2004, 55, 61-95.
120. Fakhrai, H.; Dorigo, O.; Shawler, D.L.; Lin, H.; Mercola, D.; Black, K.L.; Royston, I.; Sobol, R.E. Eradication of established intracranial rat gliomas by transforming growth factor beta antisense gene therapy. Proc. Natl. Acad. Sci. USA, 1996, 93(7), 2909-2914.
121. Fakhrai, H.; Mantil, J.C.; Liu, L.; Nicholson, G.L.; Murphy-Satter, C.S.; Ruppert, J.; Shawler, D.L. Phase I clinical trial of a TGF-beta antisense-modified tumor cell vaccine in patients with advanced glioma. Cancer Gene. Ther., 2006, 13(12), 1052-1060.
122. Hau, P.; Jachimczak, P.; Schlingensiepen, R.; Schulmeyer, F.; Jauch, T.; Steinbrecher, A.; Brawanski, A.; Proescholdt, M.; Schlaier, J.; Buchroithner, J.; Pichler, J.; Wurm, G.; Mehdorn, M.; Strege, R.; Schuierer, G.; Villarrubia, V.; Fellner, F.; Jansen, O.; Straube, T.; Nohria, V.; Goldbrunner, M.; Kunst, M.; Schmaus, S.; Stauder, G.; Bogdahn, U.; Schlingensiepen, K.H. Inhibition of TGF-beta2 with AP 12009 in recurrent malignant gliomas: from preclinical to phase I/II studies. Oligonucleotides, 2007, 17(2), 201-212.
123. Bogdahn, U.; Hau, P.; Stockhammer, G.; Venkataramana, N.K.; Mahapatra, A.K.; Suri, A.; Balasubramaniam, A.; Nair, S.; Oliushine, V.; Parfenov, V.; Poverennova, I.; Zaaroor, M.; Jachimczak, P.; Ludwig, S.; Schmaus, S.; Heinrichs, H.; Schlingensiepen, K.H. Targeted therapy for high-grade glioma with the TGF-beta2 inhibitor trabedersen: results of a randomized and controlled phase IIb study. Neuro Oncol., 2011, 13(1), 132-142.
124. National library of Medicine (US). Efficacy and Safety of AP 12009 in Patients With Recurrent or Refractory Anaplastic Astrocytoma (SAPPHIRE) 2008. http://clinicaltrials.gov/show/ NCT00761280 (Accessed Feb 7, 2011).
125. National library of Medicine (US). Safety and Tolerability of AP 12009, Administered I.V. in Patients With Advanced Tumors Known to Overproduce TGF-beta-2 2009. http://clinicaltrials.gov/ show/NCT00844064 (Accessed Feb 7, 2011).
126. Schlingensiepen, K.H. The TGF-β1 antisense oligonucleotide AP 11014 for the treatment of non-small cell lung, colorectal and prostate cancer: preclinical studies. Abstract #3132. Am. Soc. Clin. Oncol. Ann. Meet., 2004.
127. National library of Medicine (US). Phase I Trial of TGFB2-Antisense-GMCSF Gene Modified Autologous Tumor Cell (TAG) Vaccine for Advanced Cancer (Auto TAG) 2008. http://clinicaltrials.gov/show/NCT00684294 (Accessed Feb 7, 2011).
128. Arteaga, C.L. Inhibition of TGFbeta signaling in cancer therapy. Curr. Opin. Genet. Dev., 2006, 16(1), 30-37.
129. Inman, G.J.; Nicolas, F.J.; Callahan, J.F.; Harling, J.D.; Gaster, L.M.; Reith, A.D.; Laping, N.J.; Hill, C.S. SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7. Mol. Pharmacol., 2002, 62(1), 65-74.
130. Laping, N.J.; Grygielko, E.; Mathur, A.; Butter, S.; Bomberger, J.; Tweed, C.; Martin, W.; Fornwald, J.; Lehr, R.; Harling, J.; Gaster, L.; Callahan, J.F.; Olson, B.A. Inhibition of transforming growth factor (TGF)-beta1-induced extracellular matrix with a novel inhibitor of the TGF-beta type I receptor kinase activity: SB-431542. Mol. Pharmacol., 2002, 62(1), 58-64.
131. Ehata, S.; Hanyu, A.; Fujime, M.; Katsuno, Y.; Fukunaga, E.; Goto, K.; Ishikawa, Y.; Nomura, K.; Yokoo, H.; Shimizu, T.; Ogata, E.; Miyazono, K.; Shimizu, K.; Imamura, T. Ki26894, a novel transforming growth factor-beta type I receptor kinase inhibitor, inhibits in vitro invasion and in vivo bone metastasis of a human breast cancer cell line. Cancer Sci., 2007, 98(1), 127-133.
132. Bandyopadhyay, A.; Agyin, J.K.; Wang, L.; Tang, Y.; Lei, X.; Story, B.M.; Cornell, J.E.; Pollock, B.H.; Mundy, G.R.; Sun, L.Z. Inhibition of pulmonary and skeletal metastasis by a transforming growth factor-beta type I receptor kinase inhibitor. Cancer Res., 2006, 66(13), 6714-6721.
133. Subramanian, G.; Schwarz, R.E.; Higgins, L.; McEnroe, G.; Chakravarty, S.; Dugar, S.; Reiss, M. Targeting endogenous transforming growth factor beta receptor signaling in SMAD4-deficient human pancreatic carcinoma cells inhibits their invasive phenotype1. Cancer Res., 2004, 64(15), 5200-5211.
134. Ge, R.; Rajeev, V.; Ray, P.; Lattime, E.; Rittling, S.; Medicherla, S.; Protter, A.; Murphy, A.; Chakravarty, J.; Dugar, S.; Schreiner, G.; Barnard, N.; Reiss, M. Inhibition of growth and metastasis of mouse mammary carcinoma by selective inhibitor of transforming growth factor-beta type I receptor kinase in vivo. Clin. Cancer Res., 2006, 12(14 Pt 1), 4315-4330.
135. Uhl, M.; Aulwurm, S.; Wischhusen, J.; Weiler, M.; Ma, J.Y.; Almirez, R.; Mangadu, R.; Liu, Y.W.; Platten, M.; Herrlinger, U.; Murphy, A.; Wong, D.H.; Wick, W.; Higgins, L.S.; Weller, M. SD-208, a novel transforming growth factor beta receptor I kinase inhibitor, inhibits growth and invasiveness and enhances immunogenicity of murine and human glioma cells in vitro and in vivo. Cancer Res., 2004, 64(21), 7954-7961.
136. Gaspar, N.J.; Li, L.; Kapoun, A.M.; Medicherla, S.; Reddy, M.; Li, G.; O'Young, G.; Quon, D.; Henson, M.; Damm, D.L.; Muiru, G.T.; Murphy, A.; Higgins, L.S.; Chakravarty, S.; Wong, D.H. Inhibition of transforming growth factor beta signaling reduces pancreatic adenocarcinoma growth and invasiveness. Mol. Pharmacol., 2007, 72(1), 152-161.
137. Fournier, P.J.; Mohammad, K.S.; McKenna, C.R.; Peng, X.; Chirgwin, J.M.; Guise, T.A. TGF-beta blockade inhibits osteolytic metastases but not osteoblastic prostate cancer metastases. #SA274. American Society for Bone and Mineral Research 30th annual meeting, 2008.
138. Guise, T.A.; Mohammad, K.S.; Clines, G.; Stebbins, E.G.; Wong, D.H.; Higgins, L.S.; Vessella, R.; Corey, E.; Padalecki, S.; Suva, L.; Chirgwin, J.M. Basic mechanisms responsible for osteolytic and osteoblastic bone metastases. Clin. Cancer Res., 2006, 12(20 Pt 2), 6213s-6216s.
139. Zhang, B.; Halder, S.K.; Zhang, S.; Datta, P.K. Targeting transforming growth factor-beta signaling in liver metastasis of colon cancer. Cancer Lett, 2009, 277(1), 114-120.
140. Melisi, D.; Ishiyama, S.; Sclabas, G.M.; Fleming, J.B.; Xia, Q.; Tortora, G.; Abbruzzese, J.L.; Chiao, P.J. LY2109761, a novel transforming growth factor beta receptor type I and type II dual inhibitor, as a therapeutic approach to suppressing pancreatic cancer metastasis. Mol. Cancer Ther., 2008, 7(4), 829-840.
141. Calvo-Aller, E.; Baselga, J.; Glatt, S.; Cleverly, A.; Lahn, M.; C.L., A.; Rothenberg, M.L.; Carducci, M.A. First human dose escalation study in patients with metastatic malignancies to determine safety and pharmacokinetics of LY2157299, a small molecule inhibitor of the transforming growth factor-beta receptor I kinase. J. Clin. Oncol., 2008, 26(15S), 14554 (abstract).
142. Cui, Q.; Lim, S.K.; Zhao, B.; Hoffmann, F.M. Selective inhibition of TGF-beta responsive genes by Smad-interacting peptide aptamers from FoxH1, Lef1 and CBP. Oncogene, 2005, 24(24), 3864-3874.
143. Zhao, B.M.; Hoffmann, F.M. Inhibition of transforming growth factor-beta1-induced signaling and epithelial-to-mesenchymal transition by the Smad-binding peptide aptamer Trx-SARA. Mol. Biol. Cell, 2006, 17(9), 3819-3831.
144. Chen, D.; Zhao, M.; Mundy, G.R. Bone morphogenetic proteins. Growth Factors, 2004, 22(4), 233-241.
145. ten Dijke, P. Bone morphogenetic protein signal transduction in bone. Curr. Med. Res. Opin., 2006, 22 (Suppl 1), S7-11.
146. Dudley, A.T.; Lyons, K.M.; Robertson, E.J. A requirement for bone morphogenetic protein-7 during development of the mammalian kidney and eye. Genes. Dev., 1995, 9(22), 2795-2807.
147. Luo, G.; Hofmann, C.; Bronckers, A.L.; Sohocki, M.; Bradley, A.; Karsenty, G. BMP-7 is an inducer of nephrogenesis, and is also required for eye development and skeletal patterning. Genes. Dev., 1995, 9(22), 2808-2820.
148. Simic, P.; Vukicevic, S. Bone morphogenetic proteins in development and homeostasis of kidney. Cytokine Growth Factor Rev., 2005, 16(3), 299-308.
149. Buijs, J.T.; Henriquez, N.V.; van Overveld, P.G.; van der Horst, G.; Que, I.; Schwaninger, R.; Rentsch, C.; Ten Dijke, P.; Cleton- Jansen, A.M.; Driouch, K.; Lidereau, R.; Bachelier, R.; Vukicevic, S.; Clezardin, P.; Papapoulos, S.E.; Cecchini, M.G.; Lowik, C.W.; van der Pluijm, G. Bone morphogenetic protein 7 in the development and treatment of bone metastases from breast cancer. Cancer Res., 2007, 67(18), 8742-8751.
150. Buijs, J.T.; Rentsch, C.A.; van der Horst, G.; van Overveld, P.G.; Wetterwald, A.; Schwaninger, R.; Henriquez, N.V.; Ten Dijke, P.; Borovecki, F.; Markwalder, R.; Thalmann, G.N.; Papapoulos, S.E.; Pelger, R.C.; Vukicevic, S.; Cecchini, M.G.; Lowik, C.W.; van der Pluijm, G. BMP7, a putative regulator of epithelial homeostasis in the human prostate, is a potent inhibitor of prostate cancer bone metastasis in vivo. Am. J. Pathol., 2007, 171(3), 1047-1057.
151. Gautschi, O.P.; Frey, S.P.; Zellweger, R. Bone morphogenetic proteins in clinical applications. ANZ J Surg., 2007, 77(8), 626-631.
152. National Cancer Institute (NCI). Topical Halofuginone Hydrobromide in Treating Patients With HIV-Related Kaposi's Sarcoma 2009. http://clinicaltrials.gov/ct2/show/NCT00064142 (Accessed Feb 7, 2011)
153. Juarez, P.; Chirgwin, J.; Mohammad, K.S.; Ryan, C.; Walton, H.; Niewolna, M.; Mauviel, A.; Guise, T.A. Halofuginone decreases osteolytic bone metastases. M00110. J. Bone Miner. Res., 2009, 24.
154. Gadir, N.; Jackson, D.N.; Lee, E.; Foster, D.A. Defective TGF-beta signaling sensitizes human cancer cells to rapamycin. Oncogene, 2008, 27(8), 1055-1062.
155. Filyak, Y.; Filyak, O.; Stoika, R. Transforming growth factor beta- 1 enhances cytotoxic effect of doxorubicin in human lung adenocarcinoma cells of A549 line. Cell Biol. Int., 2007, 31(8), 851-855.
156. Taniguchi, Y.; Kawano, K.; Minowa, T.; Sugino, T.; Shimojo, Y.; Maitani, Y. Enhanced antitumor efficacy of folate-linked liposomal doxorubicin with TGF-beta type I receptor inhibitor. Cancer Sci., 2010, 101(10), 7.
157. Mohammad, K.S.; Stebbins, E.G.; Kingsley, L.; Fournier, P.G.J.; Niewolna, M.; McKenna, C.R.; Peng, X.; Higgins, L.; Wong, D.; Guise, T.A. Combined transforming growth factor b receptor i kinase inhibitor and biphosphonates are additve to reduce breastcancer bone metastases. J. Bone Miner. Res., 2008, 23, F275 (abstract).
158. Won, J.; Kim, H.; Park, E.J.; Hong, Y.; Kim, S.J.; Yun, Y. Tumorigenicity of mouse thymoma is suppressed by soluble type II transforming growth factor beta receptor therapy. Cancer Res., 1999, 59(6), 1273-1277
159. Dasch, J.R.; Pace, D.R.; Waegell, W.; Inenaga, D.; Ellingsworth, L. Monoclonal antibodies recognizing transforming growth factorbeta. Bioactivity neutralization and transforming growth factor beta 2 affinity purification. J. Immunol., 1989, 142(5), 1536-1541.
160. Ganapathy, V.; Ge, R.; Grazioli, A.; Xie, W.; Banach-Petrosky, W.; Kang, Y.; Lonning, S.; McPherson, J.; Yingling, J.M.; Biswas, S.; Mundy, G.R.; Reiss, M. Targeting the Transforming Growth Factor-beta pathway inhibits human basal-like breast cancer metastasis. Mol. Cancer, 2010, 9, 122.
161. Biswas, S.; Guix, M.; Rinehart, C.; Dugger, T.C.; Chytil, A.; Moses, H.L.; Freeman, M.L.; Arteaga, C.L. Inhibition of TGF-beta with neutralizing antibodies prevents radiation-induced acceleration of metastatic cancer progression. J. Clin. Invest., 2007, 117(5), 1305-1313.
162. National Library of Medicine (US). Efficacy and Safety of AP 12009 in Patients With Recurrent or Refractory Anaplastic Astrocytoma (SAPPHIRE). 2008. http://clinicaltrials.gov/ show/NCT00761280 (Accessed Feb 7, 2011).
163. National Library of Medicine (US). Safety and Tolerability of AP 12009, Administered I.V. in Patients With Advanced Tumors Known to Overproduce TGF-beta-2. 2009. http://clinicaltrials.gov/ show/NCT00844064 (Accessed Feb 7, 2011).
164. Tojo, M.; Hamashima, Y.; Hanyu, A.; Kajimoto, T.; Saitoh, M.; Miyazono, K.; Node, M.; Imamura, T. The ALK-5 inhibitor A-83- 01 inhibits Smad signaling and epithelial-to-mesenchymal transition by transforming growth factor-beta. Cancer Sci., 2005, 96(11), 791-800.
165. Petersen, M.; Thorikay, M.; Deckers, M.; van Dinther, M.; Grygielko, E.T.; Gellibert, F.; de Gouville, A.C.; Huet, S.; ten Dijke, P.; Laping, N.J. Oral administration of GW788388, an inhibitor of TGF-beta type I and II receptor kinases, decreases renal fibrosis. Kidney Int., 2008, 73(6), 705-715.
166. Lee, G.T.; Hong, J.H.; Mueller, T.J.; Watson, J.A.; Kwak, C.; Sheen, Y.Y.; Kim, D.K.; Kim, S.J.; Kim, I.Y. Effect of IN-1130, a small molecule inhibitor of transforming growth factor-beta type I receptor/activin receptor-like kinase-5, on prostate cancer cells. J. Urol., 2008, 180(6), 2660-2667.
167. Peng, S.B.; Yan, L.; Xia, X.; Watkins, S.A.; Brooks, H.B.; Beight, D.; Herron, D.K.; Jones, M.L.; Lampe, J.W.; McMillen, W.T.; Mort, N.; Sawyer, J.S.; Yingling, J.M. Kinetic characterization of novel pyrazole TGF-beta receptor I kinase inhibitors and their blockade of the epithelial-mesenchymal transition. Biochemistry, 2005, 44(7), 2293-2304.
168. Sawyer, J.S.; Beight, D.W.; Britt, K.S.; Anderson, B.D.; Campbell, R.M.; Goodson, T., Jr.; Herron, D.K.; Li, H.Y.; McMillen, W.T.; Mort, N.; Parsons, S.; Smith, E.C.; Wagner, J.R.; Yan, L.; Zhang, F.; Yingling, J.M. Synthesis and activity of new aryl- and heteroaryl-substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole inhibitors of the transforming growth factor-beta type I receptor kinase domain. Bioorg. Med. Chem. Lett., 2004, 14(13), 3581-3584.
169. Halder, S.K.; Beauchamp, R.D.; Datta, P.K. A specific inhibitor of TGF-beta receptor kinase, SB-431542, as a potent antitumor agent for human cancers. Neoplasia, 2005, 7(5), 509-521.
170. DaCosta Byfield, S.; Major, C.; Laping, N.J.; Roberts, A.B. SB-505124 is a selective inhibitor of transforming growth factor-beta type I receptors ALK4, ALK5, and ALK7. Mol. Pharmacol., 2004, 65(3), 744-752.
171. Bonniaud, P.; Margetts, P.J.; Kolb, M.; Schroeder, J.A.; Kapoun, A.M.; Damm, D.; Murphy, A.; Chakravarty, S.; Dugar, S.; Higgins, L.; Protter, A.A.; Gauldie, J. Progressive transforming growth factor beta1-induced lung fibrosis is blocked by an orally active ALK5 kinase inhibitor. Am. J. Respir. Crit. Care Med., 2005, 171(8), 889-898.
172. Rausch, M.P.; Hahn, T.; Ramanathapuram, L.; Bradley-Dunlop, D.; Mahadevan, D.; Mercado-Pimentel, M.E.; Runyan, R.B.; Besselsen, D.G.; Zhang, X.; Cheung, H.K.; Lee, W.C.; Ling, L.E.; Akporiaye, E.T. An orally active small molecule TGF-beta receptor I antagonist inhibits the growth of metastatic murine breast cancer. Anticancer Res., 2009, 29(6), 2099-2109.
173. Suzuki, E.; Kim, S.; Cheung, H.K.; Corbley, M.J.; Zhang, X.; Sun, L.; Shan, F.; Singh, J.; Lee, W.C.; Albelda, S.M.; Ling, L.E. A novel small-molecule inhibitor of transforming growth factor beta type I receptor kinase (SM16) inhibits murine mesothelioma tumor growth in vivo and prevents tumor recurrence after surgical resection. Cancer Res., 2007, 67(5), 2351-2359.
174. Ishida, W.; Mori, Y.; Lakos, G.; Sun, L.; Shan, F.; Bowes, S.; Josiah, S.; Lee, W.C.; Singh, J.; Ling, L.E.; Varga, J. Intracellular TGF-beta receptor blockade abrogates Smad-dependent fibroblast activation in vitro and in vivo. J. Invest. Dermatol., 2006, 126(8), 1733-1744.
175. Tran, T.T.; Uhl, M.; Ma, J.Y.; Janssen, L.; Sriram, V.; Aulwurm, S.; Kerr, I.; Lam, A.; Webb, H.K.; Kapoun, A.M.; Kizer, D.E.; McEnroe, G.; Hart, B.; Axon, J.; Murphy, A.; Chakravarty, S.; Dugar, S.; Protter, A.A.; Higgins, L.S.; Wick, W.; Weller, M.; Wong, D.H. Inhibiting TGF-beta signaling restores immune surveillance in the SMA-560 glioma model. Neuro. Oncol., 2007, 9(3), 259-270.
176. Wojtowicz-Praga, S.; Verma, U.N.; Wakefield, L.; Esteban, J.M.; Hartmann, D.; Mazumder, A. Modulation of B16 melanoma growth and metastasis by anti-transforming growth factor beta antibody and interleukin-2. J. Immunother. Emphasis Tumor Immunol., 1996, 19(3), 169-175.
177. Nemunaitis, J.; Dillman, R.O.; Schwarzenberger, P.O.; Senzer, N.; Cunningham, C.; Cutler, J.; Tong, A.; Kumar, P.; Pappen, B.; Hamilton, C.; DeVol, E.; Maples, P.B.; Liu, L.; Chamberlin, T.; Shawler, D.L.; Fakhrai, H. Phase II study of belagenpumatucel-L, a transforming growth factor beta-2 antisense gene-modified allogeneic tumor cell vaccine in non-small-cell lung cancer. J. Clin. Oncol., 2006, 24(29), 4721-4730.
178. Nemunaitis, J.; Nemunaitis, M.; Senzer, N.; Snitz, P.; Bedell, C.; Kumar, P.; Pappen, B.; Maples, P.B.; Shawler, D.; Fakhrai, H.Phase II trial of Belagenpumatucel-L, a TGF-beta2 antisense gene modified allogeneic tumor vaccine in advanced non small cell lung cancer (NSCLC) patients. Cancer Gene Ther., 2009, 16(8), 620-624.
179. National library of Medicine (US). Phase I Trial of TGFB2-Antisense-GMCSF Gene Modified Autologous Tumor Cell (TAG) Vaccine for Advanced Cancer (Auto TAG). 2008. http://clinicaltrials.gov/show/NCT00684294 (Accessed Feb 7, 2011).
180. Gorelik, L.; Flavell, R.A. Abrogation of TGFbeta signaling in T cells leads to spontaneous T cell differentiation and autoimmune disease. Immunity, 2000, 12(2), 171-181.
181. Kulkarni, A.B.; Huh, C.G.; Becker, D.; Geiser, A.; Lyght, M.; Flanders, K.C.; Roberts, A.B.; Sporn, M.B.; Ward, J.M.; Karlsson, S. Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death. Proc. Natl. Acad. Sci. USA, 1993, 90(2), 770-774.
182. Shull, M.M.; Ormsby, I.; Kier, A.B.; Pawlowski, S.; Diebold, R.J.; Yin, M.; Allen, R.; Sidman, C.; Proetzel, G.; Calvin, D. Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature, 1992, 359(6397), 693-699.
183. Yaswen, L.; Kulkarni, A.B.; Fredrickson, T.; Mittleman, B.; Schiffman, R.; Payne, S.; Longenecker, G.; Mozes, E.; Karlsson, S. Autoimmune manifestations in the transforming growth factor-beta 1 knockout mouse. Blood, 1996, 87(4), 1439-1445.
184. Bhowmick, N.A.; Chytil, A.; Plieth, D.; Gorska, A.E.; Dumont, N.; Shappell, S.; Washington, M.K.; Neilson, E.G.; Moses, H.L. TGFbeta signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia. Science, 2004, 303(5659), 848-851.
185. Cheng, N.; Chytil, A.; Shyr, Y.; Joly, A.; Moses, H.L. Transforming growth factor-beta signaling-deficient fibroblasts enhance hepatocyte growth factor signaling in mammary carcinoma cells to promote scattering and invasion. Mol. Cancer Res., 2008, 6(10), 1521-1533.
186. Prud'homme, G.J. Pathobiology of transforming growth factor beta in cancer, fibrosis and immunologic disease, and therapeutic considerations. Lab. Invest., 2007, 87(11), 1077-1091.
187. Klopcic, B.; Maass, T.; Meyer, E.; Lehr, H.A.; Metzger, D.; Chambon, P.; Mann, A.; Blessing, M. TGF-beta superfamily signaling is essential for tooth and hair morphogenesis and differentiation. Eur. J. Cell Biol., 2007, 86(11-12), 781-799.
188. Ruzek, M.C.; Hawes, M.; Pratt, B.; McPherson, J.; Ledbetter, S.; Richards, S.M.; Garman, R.D. Minimal effects on immune parameters following chronic anti-TGF-beta monoclonal antibody administration to normal mice. Immunopharmacol. Immunotoxicol., 2003, 25(2), 235-257.
189. Siriwardena, D.; Khaw, P.T.; King, A.J.; Donaldson, M.L.; Overton, B.M.; Migdal, C.; Cordeiro, M.F. Human antitransforming growth factor beta(2) monoclonal antibody-a new modulator of wound healing in trabeculectomy: a randomized placebo controlled clinical study. Ophthalmology, 2002, 109(3), 427-431.
190. Schlingensiepen, K.H.; Schlingensiepen, R.; Steinbrecher, A.; Hau, P.; Bogdahn, U.; Fischer-Blass, B.; Jachimczak, P. Targeted tumor therapy with the TGF-beta2 antisense compound AP 12009. Cytokine Growth Factor Rev., 2006, 17(1-2), 129-139.
191. Bonafoux, D.; Lee, W.C. Strategies for TGF-beta modulation: a review of recent patents. Expert Opin. Ther. Pat., 2009, 19(12), 1759-1769.
192. Hengst, V.; Oussoren, C.; Kissel, T.; Storm, G. Bone targeting potential of bisphosphonate-targeted liposomes. Preparation, characterization and hydroxyapatite binding in vitro. Int. J. Pharm., 2007, 331(2), 224-227.
193. Petersen, M.; Pardali, E.; van der Horst, G.; Cheung, H.; van den Hoogen, C.; van der Pluijm, G.; Ten Dijke, P. Smad2 and Smad3 have opposing roles in breast cancer bone metastasis by differentially affecting tumor angiogenesis. Oncogene, 2010, 29(9), 1351-1361.
194. Dalal, B.I.; Keown, P.A.; Greenberg, A.H. Immunocytochemical localization of secreted transforming growth factor-beta 1 to the advancing edges of primary tumors and to lymph node metastases of human mammary carcinoma. Am. J. Pathol., 1993, 143(2), 381-389.
195. Padua, D.; Zhang, X.H.; Wang, Q.; Nadal, C.; Gerald, W.L.; Gomis, R.R.; Massague, J. TGFbeta primes breast tumors for lung metastasis seeding through angiopoietin-like 4. Cell, 2008, 133(1), 66-77.
196. Juarez, P.; Guise, T.A. TGF-beta in cancer and bone: Implications for treatment of bone metastases. Bone, 2010, 48(1), 23-29.