Targeting the epithelial to mesenchymal transition in glioblastoma: The emerging role of MET signaling

OncoTargets and Therapy

Volumn 7, Issue , 2014, Pages 1933-1944

  Lee, Jin Ku ^a,b   Joo, Kyeung Min ^b   Lee, Jeongwu ^c   Yoon, Yeup ^b   Nam, Do Hyun ^b  

^a Samsung Medical Center   (South Korea)

^b Sungkyunkwan University School of Medicine   (South Korea)

^c LERNER RESEARCH INSTITUTE   (United States)

Author keywords

Epithelial to mesenchymal transition; Glioblastoma multiforme; MET signaling

Indexed keywords

5 (2,6 DICHLOROBENZYLSULFONYL) 3 [3,5 DIMETHYL 4 [2 (1 PYRROLIDINYLMETHYL) 1 PYRROLIDINYLCARBONYL] 1H PYRROL 2 YLMETHYLENE] 1,3 DIHYDRO 2H INDOL 2 ONE; ANTINEOPLASTIC AGENT; CABOZANTINIB; CRIZOTINIB; K 252A; L 2G7; N (3 CHLOROPHENYL) 3 [3,5 DIMETHYL 4 (4 METHYL 1 PIPERAZINYLCARBONYL) 1H PYRROL 2 YLMETHYLENE] 2,3 DIHYDRO N METHYL 2 OXO 1H INDOLE 5 SULFONAMIDE; NK 4; OA 5D5; RILOTUMUMAB; SCATTER FACTOR; SCATTER FACTOR RECEPTOR; SGX 523; SU 11271; TIVANTINIB; UNCLASSIFIED DRUG;

CANCER INHIBITION; CANCER RESISTANCE; CANCER STEM CELL; COLON CANCER; DRUG MECHANISM; EPITHELIAL MESENCHYMAL TRANSITION; GLIOBLASTOMA; HUMAN; MOLECULAR MODEL; NONHUMAN; PROSTATE CANCER; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; STOMACH CANCER; TUMOR VOLUME;

EID: 84908220707     PISSN: None     EISSN: 11786930     Source Type: Journal    
DOI: 10.2147/OTT.S36582     Document Type: Review

References (116)

1. Wen PY, Kesari S. Malignant gliomas in adults. N Engl J Med. 2008;359(5):492-507.
2. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987-996.
3. Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10(5):459-466.
4. Ohka F, Natsume A, Wakabayashi T. Current trends in targeted therapies for glioblastoma multiforme. Neurol Res Int. 2012;2012:878425.
5. Keunen O, Johansson M, Oudin A, et al. Anti-VEGF treatment reduces blood supply and increases tumor cell invasion in glioblastoma. Proc Natl Acad Sci U S A. 2011;108(9):3749-3754.
6. Uhm JH, Ballman KV, Wu W, et al. Phase II evaluation of gefitinib in patients with newly diagnosed grade 4 astrocytoma: Mayo/North Central Cancer Treatment Group Study N0074. Int J Radiat Oncol Biol Phys. 2011;80(2):347-353.
7. Lu-Emerson C, Norden AD, Drappatz J, et al. Retrospective study of dasatinib for recurrent glioblastoma after bevacizumab failure. J Neurooncol. 2011;104(1):287-291.
8. Chi AS, Wen PY. Inhibiting kinases in malignant gliomas. Expert Opin Ther Targets. 2007;11(4):473-496.
9. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest. 2009;119(6):1420-1428.
10. Kalluri R, Neilson EG. Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest. 2003;112(12):1776-1784.
11. Arrieta O, Saavedra-Perez D, Kuri R, et al. Brain metastasis development and poor survival associated with carcinoembryonic antigen (CEA) level in advanced non-small cell lung cancer: a prospective analysis. BMC Cancer. 2009;9:119.
12. Tso CL, Shintaku P, Chen J, et al. Primary glioblastomas express mesenchymal stem-like properties. Mol Cancer Res. 2006;4(9):607-619.
13. Freije WA, Castro-Vargas FE, Fang Z, et al. Gene expression profiling of gliomas strongly predicts survival. Cancer Res. 2004;64(18): 6503-6510.
14. Elias MC, Tozer KR, Silber JR, et al. TWIST is expressed in human gliomas and promotes invasion. Neoplasia. 2005;7(9):824-837.
15. Organ SL, Tsao MS. An overview of the c-MET signaling pathway. Ther Adv Med Oncol. 2011;3(Suppl 1):S7-S19.
16. Nakamura T, Nishizawa T, Hagiya M, et al. Molecular cloning and expression of human hepatocyte growth factor. Nature. 1989;342(6248):440-443.
17. Basilico C, Arnesano A, Galluzzo M, Comoglio PM, Michieli P. A high affinity hepatocyte growth factor-binding site in the immunoglobulin-like region of MET. J Biol Chem. 2008;283(30):21267-21277.
18. Abounader R, Laterra J. Scatter factor/hepatocyte growth factor in brain tumor growth and angiogenesis. Neuro Oncol. 2005;7(4):436-451.
19. Joo KM, Jin J, Kim E, et al. MET signaling regulates glioblastoma stem cells. Cancer Res. 2012;72(15):3828-3838.
20. De Bacco F, Casanova E, Medico E, et al. The MET oncogene is a functional marker of a glioblastoma stem cell subtype. Cancer Res. 2012;72(17):4537-4550.
21. Boccaccio C, Comoglio PM. The MET oncogene in glioblastoma stem cells: implications as a diagnostic marker and a therapeutic target. Cancer Res. 2013;73(11):3193-3199.
22. Thiery JP. Epithelial-mesenchymal transitions in development and pathologies. Curr Opin Cell Biol. 2003;15(6):740-746.
23. Aybar MJ, Nieto MA, Mayor R. Snail precedes Slug in the genetic cascade required for the specification and migration of the Xenopus neural crest. Development. 2003;130(3):483-494.
24. Eitner F, Floege J. Novel insights into renal fibrosis. Curr Opin Nephrol Hypertens. 2003;12(3):227-232.
25. Yanez-Mo M, Lara-Pezzi E, Selgas R, et al. Peritoneal dialysis and epithelial-to-mesenchymal transition of mesothelial cells. N Engl J Med. 2003;348(5):403-413.
26. Saika S, Miyamoto T, Tanaka S, et al. Response of lens epithelial cells to injury: role of lumican in epithelial-mesenchymal transition. Invest Ophthalmol Vis Sci. 2003;44(5):2094-2102.
27. Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer. 2002;2(6):442-454.
28. Xue C, Plieth D, Venkov C, Xu C, Neilson EG. The gatekeeper effect of epithelial-mesenchymal transition regulates the frequency of breast cancer metastasis. Cancer Res. 2003;63(12):3386-3394.
29. Lee TK, Poon RT, Yuen AP, et al. Twist overexpression correlates with hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition. Clin Cancer Res. 2006;12(18):5369-5376.
30. Tsukamoto H, Shibata K, Kajiyama H, Terauchi M, Nawa A, Kikkawa F. Irradiation-induced epithelial-mesenchymal transition (EMT) related to invasive potential in endometrial carcinoma cells. Gynecol Oncol. 2007;107(3):500-504.
31. Kajiyama H, Shibata K, Terauchi M, et al. Chemoresistance to paclitaxel induces epithelial-mesenchymal transition and enhances metastatic potential for epithelial ovarian carcinoma cells. Int J Oncol. 2007;31(2):277-283.
32. Kurrey NK, Jalgaonkar SP, Joglekar AV, et al. Snail and Slug mediate radioresistance and chemoresistance by antagonizing p53-mediated apoptosis and acquiring a stem-like phenotype in ovarian cancer cells. Stem Cells. 2009;27(9):2059-2068.
33. Rosano L, Cianfrocca R, Spinella F, et al. Acquisition of chemoresistance and EMT phenotype is linked with activation of the endothelin A receptor pathway in ovarian carcinoma cells. Clin Cancer Res. 2011;17(8):2350-2360.
34. Lim S, Becker A, Zimmer A, Lu J, Buettner R, Kirfel J. SNAI1-mediated epithelial-mesenchymal transition confers chemoresistance and cellular plasticity by regulating genes involved in cell death and stem cell maintenance. PloS One. 2013;8(6):e66558.
35. Suda K, Tomizawa K, Fujii M, et al. Epithelial to mesenchymal transition in an epidermal growth factor receptor-mutant lung cancer cell line with acquired resistance to erlotinib. J Thorac Oncol. 2011;6(7):1152-1161.
36. Krysan K, Lee JM, Dohadwala M, et al. Inflammation, epithelial to mesenchymal transition, and epidermal growth factor receptor tyrosine kinase inhibitor resistance. J Thorac Oncol. 2008;3(2):107-110.
37. Hennessy BT, Gonzalez-Angulo AM, Stemke-Hale K, et al. Characterization of a naturally occurring breast cancer subset enriched in epithelial-to-mesenchymal transition and stem cell characteristics. Cancer Res. 2009;69(10):4116-4124.
38. Stingl J, Caldas C. Molecular heterogeneity of breast carcinomas and the cancer stem cell hypothesis. Nat Rev Cancer. 2007;7(10):791-799.
39. Liao MJ, Zhang CC, Zhou B, et al. Enrichment of a population of mammary gland cells that form mammospheres and have in vivo repopulating activity. Cancer Res. 2007;67(17):8131-8138.
40. Mani SA, Guo W, Liao MJ, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133(4): 704-715.
41. Morel AP, Lievre M, Thomas C, Hinkal G, Ansieau S, Puisieux A. Generation of breast cancer stem cells through epithelial-mesenchymal transition. PloS One. 2008;3(8):e2888.
42. 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.
43. Jechlinger M, Grunert S, Tamir IH, et al. Expression profiling of epithelial plasticity in tumor progression. Oncogene. 2003;22(46):7155-7169.
44. Yang J, Weinberg RA. Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell. 2008;14(6): 818-829.
45. Tse JC, Kalluri R. Mechanisms of metastasis: epithelial-to-mesenchymal transition and contribution of tumor microenvironment. J Cell Biochem. 2007;101(4):816-829.
46. Miyazono K. TGF-beta signaling by Smad proteins. Cytokine Growth Factor Rev. 2000;11(1-2):15-22.
47. Miyazono K. TGF-beta/SMAD signaling and its involvement in tumor progression. Biol Pharm Bull. 2000;23(10):1125-1130.
48. Bhowmick NA, Zent R, Ghiassi M, McDonnell M, Moses HL. Integrin beta 1 signaling is necessary for transforming growth factor-beta activation of p38MAPK and epithelial plasticity. J Biol Chem. 2001;276(50):46707-46713.
49. Bhowmick NA, Ghiassi M, Bakin A, et al. Transforming growth factor-beta1 mediates epithelial to mesenchymal transdifferentiation through a RhoA-dependent mechanism. Mol Biol Cell. 2001;12(1):27-36.
50. Kim K, Lu Z, Hay ED. Direct evidence for a role of beta-catenin/LEF-1 signaling pathway in induction of EMT. Cell Biol Int. 2002;26(5): 463-476.
51. Medici D, Hay ED, Olsen BR. Snail and Slug promote epithelial-mesenchymal transition through beta-catenin-T-cell factor-4-dependent expression of transforming growth factor-beta3. Mol Biol Cell. 2008;19(11):4875-4887.
52. Vandewalle C, Comijn J, De Craene B, et al. SIP1/ZEB2 induces EMT by repressing genes of different epithelial cell-cell junctions. Nucleic Acids Res. 2005;33(20):6566-6578.
53. Comijn J, Berx G, Vermassen P, et al. The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Mol Cell. 2001;7(6):1267-1278.
54. Ansieau S, Bastid J, Doreau A, et al. Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence. Cancer Cell. 2008;14(1):79-89.
55. Smit MA, Geiger TR, Song JY, Gitelman I, Peeper DS. A Twist-Snail axis critical for TrkB-induced epithelial-mesenchymal transition-like transformation, anoikis resistance, and metastasis. Mol Cell Biol. 2009;29(13):3722-3737.
56. Xie G, Yao Q, Liu Y, et al. IL-6-induced epithelial-mesenchymal transition promotes the generation of breast cancer stem-like cells analogous to mammosphere cultures. Int J Oncol. 2012;40(4):1171-1179.
57. Yadav A, Kumar B, Datta J, Teknos TN, Kumar P. IL-6 promotes head and neck tumor metastasis by inducing epithelial-mesenchymal transition via the JAK-STAT3-SNAIL signaling pathway. Mol Cancer Res. 2011;9(12):1658-1667.
58. Su YW, Xie TX, Sano D, Myers JN. IL-6 stabilizes Twist and enhances tumor cell motility in head and neck cancer cells through activation of casein kinase 2. PloS One. 2011;6(4):e19412.
59. Priester M, Copanaki E, Vafaizadeh V, et al. STAT3 silencing inhibits glioma single cell infiltration and tumor growth. Neuro Oncol. 2013;15(7):840-852.
60. Zarkoob H, Taube JH, Singh SK, Mani SA, Kohandel M. Investigating the link between molecular subtypes of glioblastoma, epithelial-mesenchymal transition, and CD133 cell surface protein. PloS One. 2013;8(5):e64169.
61. Motta FJ, Valera ET, Lucio-Eterovic AK, et al. Differential expression of E-cadherin gene in human neuroepithelial tumors. Genet Mol Res. 2008;7(2):295-304.
62. Han SP, Kim JH, Han ME, et al. SNAI1 is involved in the proliferation and migration of glioblastoma cells. Cell Mol Neurobiol. 2011;31(3):489-496.
63. Xia M, Hu M, Wang J, et al. Identification of the role of Smad interacting protein 1 (SIP1) in glioma. J Neurooncol. 2010;97(2):225-232.
64. Honczarenko M, Le Y, Swierkowski M, Ghiran I, Glodek AM, Silberstein LE. Human bone marrow stromal cells express a distinct set of biologically functional chemokine receptors. Stem Cells. 2006;24(4): 1030-1041.
65. Zhu Y, Yang P, Wang Q, et al. The effect of CXCR4 silencing on epithelial-mesenchymal transition related genes in glioma U87 cells. Anat Rec. 2013;296(12):1850-1856.
66. Comoglio PM, Giordano S, Trusolino L. Drug development of MET inhibitors: targeting oncogene addiction and expedience. Nat Rev Drug Discov. 2008;7(6):504-516.
67. Trusolino L, Comoglio PM. Scatter-factor and semaphorin receptors: cell signalling for invasive growth. Nat RevCancer. 2002;2(4):289-300.
68. Stoker M, Gherardi E, Perryman M, Gray J. Scatter factor is a fibroblast-derived modulator of epithelial cell mobility. Nature. 1987;327(6119): 239-242.
69. Rodrigues GA, Park M. Autophosphorylation modulates the kinase activity and oncogenic potential of the MET receptor tyrosine kinase. Oncogene. 1994;9(7):2019-2027.
70. Ponzetto C, Bardelli A, Zhen Z, et al. A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family. Cell. 1994;77(2):261-271.
71. Fixman ED, Fournier TM, Kamikura DM, Naujokas MA, Park M. Pathways downstream of Shc and Grb2 are required for cell transformation by the Tpr-MET oncoprotein. J Biol Chem. 1996;271(22):13116-13122.
72. Koch A, Mancini A, El Bounkari O, Tamura T. The SH2-domian-containing inositol 5-phosphatase (SHIP)-2 binds to c-MET directly via tyrosine residue 1356 and involves hepatocyte growth factor (HGF)-induced lamellipodium formation, cell scattering and cell spreading. Oncogene. 2005;24(21):3436-3447.
73. Boccaccio C, Ando M, Tamagnone L, et al. Induction of epithelial tubules by growth factor HGF depends on the STAT pathway. Nature. 1998;391(6664):285-288.
74. Organ SL, Tong J, Taylor P, et al. Quantitative phospho-proteomic profiling of hepatocyte growth factor (HGF)-MET signaling in colorectal cancer. J Proteome Res. 2011;10(7):3200-3211.
75. Hammond DE, Hyde R, Kratchmarova I, Beynon RJ, Blagoev B, Clague MJ. Quantitative analysis of HGF and EGF-dependent phosphotyrosine signaling networks. J Proteome Res. 2010;9(5):2734-2742.
76. Boccaccio C, Comoglio PM. Invasive growth: a MET-driven genetic programme for cancer and stem cells. Nat Rev Cancer. 2006;6(8): 637-645.
77. Montesano R, Matsumoto K, Nakamura T, Orci L. Identification of a fibroblast-derived epithelial morphogen as hepatocyte growth factor. Cell. 1991;67(5):901-908.
78. Andermarcher E, Surani MA, Gherardi E. Co-expression of the HGF/SF and c-MET genes during early mouse embryogenesis precedes reciprocal expression in adjacent tissues during organogenesis. Dev Genet. 1996;18(3):254-266.
79. Song W, Majka SM, McGuire PG. Hepatocyte growth factor expression in the developing myocardium: evidence for a role in the regulation of the mesenchymal cell phenotype and urokinase expression. Dev Dyn. 1999;214(1):92-100.
80. Maina F, Klein R. Hepatocyte growth factor, a versatile signal for developing neurons. Nat Neurosci. 1999;2(3):213-217.
81. Canadas I, Rojo F, Taus A, et al. Targeting epithelial-to-mesenchymal transition with MET inhibitors reverts chemoresistance in small cell lung cancer. Clin Cancer Res. 2014;20(4):938-950.
82. Nagai T, Arao T, Furuta K, et al. Sorafenib inhibits the hepatocyte growth factor-mediated epithelial mesenchymal transition in hepatocellular carcinoma. Mol Cancer Ther. 2011;10(1):169-177.
83. Lu KV, Chang JP, Parachoniak CA, et al. VEGF inhibits tumor cell invasion and mesenchymal transition through a MET/VEGFR2 complex. Cancer Cell. 2012;22(1):21-35.
84. Lorenzato A, Olivero M, Patane S, et al. Novel somatic mutations of the MET oncogene in human carcinoma metastases activating cell motility and invasion. Cancer Res. 2002;62(23):7025-7030.
85. Di Renzo MF, Olivero M, Martone T, et al. Somatic mutations of the MET oncogene are selected during metastatic spread of human HNSC carcinomas. Oncogene. 2000;19(12):1547-1555.
86. Rong S, Segal S, Anver M, Resau JH, Vande Woude GF. Invasiveness and metastasis of NIH 3T3 cells induced by MET-hepatocyte growth factor/scatter factor autocrine stimulation. Proc Natl Acad Sci U S A. 1994;91(11):4731-4735.
87. Rahimi N, Tremblay E, McAdam L, Park M, Schwall R, Elliott B. Identification of a hepatocyte growth factor autocrine loop in a murine mammary carcinoma. Cell Growth Differ. 1996;7(2):263-270.
88. Navab R, Liu J, Seiden-Long I, et al. Co-overexpression of MET and hepatocyte growth factor promotes systemic metastasis in NCI-H460 non-small cell lung carcinoma cells. Neoplasia. 2009;11(12):1292-1300.
89. Engelman JA, Zejnullahu K, Mitsudomi T, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science. 2007;316(5827):1039-1043.
90. Koochekpour S, Jeffers M, Rulong S, et al. MET and hepatocyte growth factor/scatter factor expression in human gliomas. Cancer Res. 1997;57(23):5391-5398.
91. Kong DS, Song SY, Kim DH, et al. Prognostic significance of c-MET expression in glioblastomas. Cancer. 2009;115(1):140-148.
92. Liu W, Fu Y, Xu S, et al. c-MET expression is associated with time to recurrence in patients with glioblastoma multiforme. J Clin Neurosci. 2011;18(1):119-121.
93. Abounader R, Ranganathan S, Kim BY, Nichols C, Laterra J. Signaling pathways in the induction of c-MET receptor expression by its ligand scatter factor/hepatocyte growth factor in human glioblastoma. J Neurochem. 2001;76(5):1497-1508.
94. Li Y, Li A, Glas M, et al. c-MET signaling induces a reprogramming network and supports the glioblastoma stem-like phenotype. Proc Natl Acad Sci U S A. 2011;108(24):9951-9956.
95. Kim KH, Seol HJ, Kim EH, et al. Wnt/beta-catenin signaling is a key downstream mediator of MET signaling in glioblastoma stem cells. Neuro Oncol. 2013;15(2):161-171.
96. Date K, Matsumoto K, Shimura H, Tanaka M, Nakamura T. HGF/NK4 is a specific antagonist for pleiotrophic actions of hepatocyte growth factor. FEBS Lett. 1997;420(1):1-6.
97. Matsumoto K, Nakamura T. Mechanisms and significance of bifunctional NK4 in cancer treatment. Biochem Biophys Res Commun. 2005;333(2):316-327.
98. Michieli P, Mazzone M, Basilico C, et al. Targeting the tumor and its microenvironment by a dual-function decoy MET receptor. Cancer Cell. 2004;6(1):61-73.
99. Burgess TL, Sun J, Meyer S, et al. Biochemical characterization of AMG 102: a neutralizing, fully human monoclonal antibody to human and nonhuman primate hepatocyte growth factor. Mol Cancer Ther. 2010;9(2):400-409.
100. Morotti A, Mila S, Accornero P, Tagliabue E, Ponzetto C. K252a inhibits the oncogenic properties of MET, the HGF receptor. Oncogene. 2002;21(32):4885-4893.
101. Christensen JG, Schreck R, Burrows J, et al. A selective small molecule inhibitor of c-MET kinase inhibits c-MET-dependent phenotypes in vitro and exhibits cytoreductive antitumor activity in vivo. Cancer Res. 2003;63(21):7345-7355.
102. Wang X, Le P, Liang C, et al. Potent and selective inhibitors of the MET [hepatocyte growth factor/scatter factor (HGF/SF) receptor] tyrosine kinase block HGF/SF-induced tumor cell growth and invasion. Mol Cancer Ther. 2003;2(11):1085-1092.
103. Sattler M, Pride YB, Ma P, et al. A novel small molecule met inhibitor induces apoptosis in cells transformed by the oncogenic TPR-MET tyrosine kinase. Cancer Res. 2003;63(17):5462-5469.
104. Ma PC, Jagadeeswaran R, Jagadeesh S, et al. Functional expression and mutations of c-MET and its therapeutic inhibition with SU11274 and small interfering RNA in non-small cell lung cancer. Cancer Res. 2005;65(4):1479-1488.
105. Rodig SJ, Shapiro GI. Crizotinib, a small-molecule dual inhibitor of the c-MET and ALK receptor tyrosine kinases. Curr Opin Investig Drugs. 2010;11(12):1477-1490.
106. Surriga O, Rajasekhar VK, Ambrosini G, Dogan Y, Huang R, Schwartz GK. Crizotinib, a c-MET inhibitor, prevents metastasis in a metastatic uveal melanoma model. Mol Cancer Ther. 2013;12(12):2817-2826.
107. Dai J, Zhang H, Karatsinides A, et al. Cabozantinib inhibits prostate cancer growth and prevents tumor-induced bone lesions. Clin Cancer Res. 2014;20(3):617-630.
108. Katayama R, Aoyama A, Yamori T, et al. Cytotoxic activity of tivantinib (ARQ 197) is not due solely to c-MET inhibition. Cancer Res. 2013;73(10):3087-3096.
109. Cao B, Su Y, Oskarsson M, et al. Neutralizing monoclonal antibodies to hepatocyte growth factor/scatter factor (HGF/SF) display antitumor activity in animal models. Proc Natl Acad Sci U S A. 2001;98(13):7443-7448.
110. Kim KJ, Wang L, Su YC, et al. Systemic anti-hepatocyte growth factor monoclonal antibody therapy induces the regression of intracranial glioma xenografts. Clin Cancer Res. 2006;12(4):1292-1298.
111. Burgess T, Coxon A, Meyer S, et al. Fully human monoclonal antibodies to hepatocyte growth factor with therapeutic potential against hepatocyte growth factor/c-MET-dependent human tumors. Cancer Res. 2006;66(3):1721-1729.
112. Martens T, Schmidt NO, Eckerich C, et al. A novel one-armed anti-c-MET antibody inhibits glioblastoma growth in vivo. Clin Cancer Res. 2006;12(20 Pt 1):6144-6152.
113. Xie Q, Bradley R, Kang L, et al. Hepatocyte growth factor (HGF) autocrine activation predicts sensitivity to MET inhibition in glioblastoma. Proc Natl Acad Sci U S A. 2012;109(2):570-575.
114. Zhang YW, Staal B, Essenburg C, et al. MET kinase inhibitor SGX523 synergizes with epidermal growth factor receptor inhibitor erlotinib in a hepatocyte growth factor-dependent fashion to suppress carcinoma growth. Cancer Res. 2010;70(17):6880-6890.
115. Rath P, Lal B, Ajala O, et al. In vivo c-MET pathway inhibition depletes human glioma xenografts of tumor-propagating stem-like cells. Transl Oncol. 2013;6(2):104-111.
116. Lal B, Goodwin CR, Sang Y, et al. EGFRvIII and c-MET pathway inhibitors synergize against PTEN-null/EGFRvIII+ glioblastoma xenografts. Mol Cancer Ther. 2009;8(7):1751-1760.