Suppression of Met Expression: A Possible Cancer Treatment: Commentary re: S. J. Kim et al., Reduced c-Met Expression by an Adenovirus Expressing a c-Met Ribozyme Inhibits Tumorigenic Growth and Lymph Node Metastases of PC3-LN4 Prostate Tumor Cells in an Orthotopic Nude Mouse Model. Clin. Cancer Res., 14: 5161-5170, 2003

Clinical Cancer Research

Volumn 9, Issue 14, 2003, Pages 5085-5090

  Shinomiya, Nariyoshi ^a   Vande Woude, George F ^a  

^a VAN ANDEL RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEIN TYROSINE KINASE; SCATTER FACTOR RECEPTOR; UNCLASSIFIED DRUG;

ADENOVIRUS; ANIMAL MODEL; CANCER INVASION; CANCER THERAPY; CARCINOGENESIS; GENE REPRESSION; HUMAN; LYMPH NODE METASTASIS; MALE; MOUSE; NONHUMAN; NOTE; PRIORITY JOURNAL; PROSTATE CANCER; SIGNAL TRANSDUCTION;

ADENOVIRIDAE; ANIMALS; DISEASE MODELS, ANIMAL; DOWN-REGULATION; GENE THERAPY; HUMANS; LYMPHATIC METASTASIS; MALE; MICE; PROSTATIC NEOPLASMS; PROTO-ONCOGENE PROTEINS C-MET; RNA, CATALYTIC;

EID: 0242694513     PISSN: 10780432     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Note

References (80)

1. Abounader, R., Ranganathan, S., Lal, B., Fielding, K., Book, A., Dietz, H., Burger, P., and Laterra, J. Reversion of human glioblastoma malignancy by U1 small nuclear RNA/ribozyme targeting of scatter factor/hepatocyte growth factor and c-met expression. J. Natl. Cancer Inst., 91: 1548-1556, 1999.
2. Kim, S. J., Johnson, M., Koterba, K., Herynk, M. H., Uehara, H., and Gallick, G. E. Reduced c-Met expression by an adenovirus expressing a c-met ribozyme inhibits tumorigenic growth and lymph node metastases of PC3-LN4 prostate tumor cells in an orthotopic nude mouse model. Clin. Cancer Res., 14: 5160-5170 2003.
3. Cooper, C. S., Park, M., Blair, D. G., Tainsky, M. A., Huebner, K., Croce, C. M., and Vande Woude, G. F. Molecular cloning of a new transforming gene from a chemically transformed human cell line. Nature (Lond.), 311: 29-33, 1984.
4. Park, M., Dean, M., Cooper, C. S., Schmidt, M., O'Brien, S. J., Blair, D. G., and Vande Woude, G. F. Mechanism of met oncogene activation. Cell, 45: 895-904, 1986.
5. Bottaro, D. P., Rubin, J. S., Faletto, D. L., Chan, A. M., Kmiecik, T. E., Vande Woude, G. F., and Aaronson, S. A. Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science (Wash. DC), 251: 802-804, 1991.
6. Nakamura, T., Nishizawa, T., Hagiya, M., Seki, T., Shimonishi, M., Sugimura, A., Tashiro, K., and Shimizu, S. Molecular cloning and expression of human hepatocyte growth factor. Nature (Lond.), 342: 440-443, 1989.
7. Miyazawa, K., Tsubouchi, H., Naka, D., Takahashi, K., Okigaki, M., Arakaki, N., Nakayama, H., Hirono, S., Sakiyama, O., et al. Molecular cloning and sequence analysis of cDNA for human hepatocyte growth factor. Biochem. Biophys. Res. Commun., 163: 967-973, 1989.
8. Gherardi, E., Gray, J., Stoker, M., Perryman, M., and Furlong, R. Purification of scatter factor, a fibroblast-derived basic protein that modulates epithelial interactions and movement. Proc. Natl. Acad. Sci. USA, 86: 5844-5848, 1989.
9. Stoker, M., Gherardi, E., Perryman, M., and Gray, J. Scatter factor is a fibroblast-derived modulator of epithelial cell mobility. Nature (Lond.), 327: 239-242, 1987.
10. Weidner, K. M., Arakaki, N., Hartmann, G., Vandekerckhove, J., Weingart, S., Rieder, H., Fonatsch, C., Tsubouchi, H., Hishida, T., Daikuhara, Y., et al. Evidence for the identity of human scatter factor and human hepatocyte growth factor. Proc. Natl. Acad. Sci. USA, 88: 7001-7005, 1991.
11. Montesano, R., Matsumoto, K., Nakamura, T., and Orci, L. Identification of a fibroblast-derived epithelial morphogen as hepatocyte growth factor. Cell, 67: 901-908, 1991.
12. Ponzetto, C., Bardelli, A., Zhen, Z., Maina, F., dalla Zonca, P., Giordano, S., Graziani, A., Panayotou, G., and Comoglio, P. M. A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family. Cell, 77: 261-271, 1994.
13. Zhang, Y. W., and Vande Woude, G. F. HGF/SF-met signaling in the control of branching morphogenesis and invasion. J. Cell Biochem., 88: 408-417, 2003.
14. Nguyen, L., Holgado-Madruga, M., Maroun, C., Fixman, E. D., Kamikura, D., Fournier, T., Charest, A., Tremblay, M. L., Wong, A. J., and Park, M. Association of the multisubstrate docking protein Gab1 with the hepatocyte growth factor receptor requires a functional Grb2 binding site involving tyrosine 1356. J. Biol. Chem., 272: 20811-20819, 1997.
15. Birchmeier, C., and Gherardi, E. Developmental roles of HGF/SF and its receptor, the c-Met tyrosine kinase. Trends Cell Biol., 8: 404-410, 1998.
16. Xiao, G. H., Jeffers, M., Bellacosa, A., Mitsuuchi, Y., Vande Woude, G. F., and Testa, J. R. Anti-apoptotic signaling by hepatocyte growth factor/Met via the phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase pathways. Proc. Natl. Acad. Sci. USA, 98: 247-252, 2001.
17. Ponzetto, C., Zhen, Z., Audero, E., Maina, F., Bardelli, A., Basile, M. L., Giordano, S., Narsimhan, R., and Comoglio, P. Specific uncoupling of GRB2 from the Met receptor. Differential effects on transformation and motility. J. Biol. Chem., 271: 14119-14123, 1996.
18. Ridley, A. J., Comoglio, P. M., and Hall, A. Regulation of scatter factor/hepatocyte growth factor responses by Ras, Rac, and Rho in MDCK cells. Mol. Cell. Biol., 15: 1110-1122, 1995.
19. Zhang, Y-W., Su, Y., Volpert, O. V., and Vande Woude, G. F. HGF/SF mediates angiogenesis through positive VEGF and negative thrombospondin-1 regulation. Proc. Natl. Acad. Sci. USA, in press, 2003.
20. Zhang, Y. W., Wang, L. M., Jove, R., and Vande Woude, G. F. Requirement of Stat3 signaling for HGF/SF-Met mediated tumorigenesis. Oncogene, 21: 217-226, 2002.
21. Miyazawa, K., Shimomura, T., Naka, D., and Kitamura, N. Proteolytic activation of hepatocyte growth factor in response to tissue injury. J. Biol. Chem., 269: 8966-8970, 1994.
22. Rahmoune, H., Rudland, P. S., Gallagher, J. T., and Fernig, D. G. Hepatocyte growth factor/scatter factor has distinct classes of binding site in heparan sulfate from mammary cells. Biochemistry, 37: 6003-6008, 1998.
23. Grenier, A., Chollet-Martin, S., Crestani, B., Delarche, C., El Benna, J., Boutten, A., Andrieu, V., Durand, G., Gougerot-Pocidalo, M. A., Aubier, M., and Dehoux, M. Presence of a mobilizable intracellular pool of hepatocyte growth factor in human polymorphonuclear neutrophils. Blood, 99: 2997-3004, 2002.
24. Naldini, L., Tamagnone, L., Vigna, E., Sachs, M., Hartmann, G., Birchmeier, W., Daikuhara, Y., Tsubouchi, H., Blasi, F., and Comoglio, P. M. Extracellular proteolytic cleavage by urokinase is required for activation of hepatocyte growth factor/scatter factor. EMBO J., 11: 4825-4833, 1992.
25. Naka, D., Ishii, T., Yoshiyama, Y., Miyazawa, K., Hara, H., Hishida, T., and Kidamura, N. Activation of hepatocyte growth factor by proteolytic conversion of a single chain form to a heterodimer. J. Biol. Chem., 267: 20114-20119, 1992.
26. Uehara, Y., Minowa, O., Mori, C., Shiota, K., Kuno, J., Noda, T., and Kitamura, N. Placental defect and embryonic lethality in mice lacking hepatocyte growth factor/scatter factor. Nature (Lond.), 373: 702-705, 1995.
27. Schmidt, C., Bladt, F., Goedecke, S., Brinkmann, V., Zschiesche, W., Sharpe, M., Gherardi, E., and Birchmeier, C. Scatter factor/hepatocyte growth factor is essential for liver development. Nature (Lond.), 373: 699-702, 1995.
28. Bladt, F., Riethmacher, D., Isenmann, S., Aguzzi, A., and Birchmeier, C. Essential role for the c-met receptor in the migration of myogenic precursor cells into the limb bud. Nature (Lond.), 376: 768-771, 1995.
29. Ebens, A., Brose, K., Leonardo, E. D., Hanson, M. G., Jr., Bladt, F., Birchmeier, C., Barres, B. A., and Tessier-Lavigne, M. Hepatocyte growth factor/scatter factor is an axonal chemoattractant and a neurotrophic factor for spinal motor neurons. Neuron, 17: 1157-1172, 1996.
30. Stewart, F. Roles of mesenchymal-epithelial interactions and hepatocyte growth factor-scatter factor (HGF-SF) in placental development. Rev. Reprod., 1: 144-148, 1996.
31. Nakamura, T., Mizuno, S., Matsumoto, K., Sawa, Y., and Matsuda, H. Myocardial protection from ischemia/reperfusion injury by endogenous and exogenous HGF. J. Clin. Investig., 106: 1511-1519, 2000.
32. Michalopoulos, G. K., and DeFrances, M. C. Liver regeneration. Science (Wash. DC), 276: 60-66, 1997.
33. Rabkin, R., Fervenza, F., Tsao, T., Sibley, R., Friedlaender, M., Hsu, F., Lassman, C., Hausmann, M., Huie, P., and Schwall, R. H. Hepatocyte growth factor receptor in acute tubular necrosis. J. Am. Soc. Nephrol., 12: 531-540, 2001.
34. Ueki, T., Kaneda, Y., Tsutsui, H., Nakanishi, K., Sawa, Y., Morishita, R., Matsumoto, K., Nakamura, T., Takahashi, H., Okamoto, E., and Fujimoto, J. Hepatocyte growth factor gene therapy of liver cirrhosis in rats. Nat. Med., 5: 226-230, 1999.
35. Vande Woude, G. F., Jeffers, M., Cortner, J., Alvord, G., Tsarfaty, I., and Resau, J. Met-HGF/SF: tumorigenesis, invasion and metastasis. Ciba Found. Symp. 212: 119-132, 1997.
36. Recio, J. A., and Merlino, G. Hepatocyte growth factor/scatter factor induces feedback up-regulation of CD44v6 in melanoma cells through Egr-1. Cancer Res., 63: 1576-1582, 2003.
37. Li, G., Schaider, H., Satyamoorthy, K., Hanakawa, Y., Hashimoto, K., and Herlyn, M. Downregulation of E-cadherin and Desmoglein 1 by autocrine hepatocyte growth factor during melanoma development. Oncogene, 20: 8125-8135, 2001.
38. Rong, S., Segal, S., Anver, M., Resau, J. H., and Vande Woude, G. F. Invasiveness and metastasis of NIH 3T3 cells induced by Methepatocyte growth factor/scatter factor autocrine stimulation. Proc. Natl. Acad. Sci. USA, 91: 4731-4735, 1994.
39. Park, W. S., Oh, R. R., Kim, Y. S., Park, J. Y., Shin, M. S., Lee, H. K., Lee, S. H., Yoo, N. J., and Lee, J. Y. Absence of mutations in the kinase domain of the Met gene and frequent expression of Met and HGF/SF protein in primary gastric carcinomas. Apmis, 108: 195-200, 2000.
40. Morello, S., Olivero, M., Aimetti, M., Bernardi, M., Berrone, S., Di Renzo, M. F., and Giordano, S. MET receptor is overexpressed but not mutated in oral squamous cell carcinomas. J. Cell Physiol., 189: 285-290, 2001.
41. Rong, S., Bodescot, M., Blair, D., Dunn, J., Nakamura, T., Mizuno, K., Park, M., Chan, A., Aaronson, S., and Vande Woude, G. F. Tumorigenicity of the met proto-oncogene and the gene for hepatocyte growth factor. Mol. Cell. Biol., 12: 5152-5158, 1992.
42. Rosen, E. M., Nigam, S. K., and Goldberg, I. D. Scatter factor and the c-met receptor: a paradigm for mesenchymal/epithelial interaction. J. Cell Biol., 127: 1783-1787, 1994.
43. Johnson, M., Koukoulis, G., Kochhar, K., Kubo, C., Nakamura, T., and Iyer, A. Selective tumorigenesis in non-parenchymal liver epithelial cell lines by hepatocyte growth factor transfection. Cancer Lett., 96: 37-48, 1995.
44. Long, I. S., Han, K., Li, M., Shirasawa, S., Sasazuki, T., Johnston, M., and Tsao, M. S. Met receptor overexpression and oncogenic Ki-ras mutation cooperate to enhance tumorigenicity of colon cancer cells in vivo. Mol. Cancer Res., 1: 393-401, 2003.
45. Jeffers, M., Rong, S., and Vande Woude, G. F. Enhanced tumorigenicity and invasion-metastasis by hepatocyte growth factor/scatter factor-met signalling in human cells concomitant with induction of the urokinase proteolysis network. Mol. Cell. Biol., 16: 1115-1125, 1996.
46. Otsuka, T., Takayama, H., Sharp, R., Celli, G., LaRochelle, W. J., Bottaro, D. P., Ellmore, N., Vieira, W., Owens, J. W., Anver, M., and Merlino, G. c-Met autocrine activation induces development of malignant melanoma and acquisition of the metastatic phenotype. Cancer Res., 58: 5157-5167, 1998.
47. Yu, Y., and Merlino, G. Constitutive c-Met signaling through a nonautocrine mechanism promotes metastasis in a transgenic transplantation model. Cancer Res., 62: 2951-2956, 2002.
48. Takayama, H., LaRochelle, W. J., Sharp, R., Otsuka, T., Kriebel, P., Anver, M., Aaronson, S. A., and Merlino, G. Diverse tumorigenesis associated with aberrant development in mice overexpressing hepatocyte growth factor/scatter factor. Proc. Natl. Acad. Sci. USA, 94: 701-706, 1997.
49. Harvey, P., Clark, I. M., Jaurand, M. C., Warn, R. M., and Edwards, D. R. Hepatocyte growth factor/scatter factor enhances the invasion of mesothelioma cell lines and the expression of matrix metalloproteinases. Br. J. Cancer, 83: 1147-1153, 2000.
50. Kermorgant, S., Aparicio, T., Dessirier, V., Lewin, M. J., and Lehy, T. Hepatocyte growth factor induces colonic cancer cell invasiveness via enhanced motility and protease overproduction. Evidence for PI3 kinase and PKC involvement. Carcinogenesis (Lond.), 22: 1035-1042, 2001.
51. Simian, M., Hirai, Y., Navre, M., Werb, Z., Lochter, A., and Bissell, M. J. The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells. Development, 128: 3117-3131, 2001.
52. Moriyama, T., Kataoka, H., Hamasuna, R., Yokogami, K., Uehara, H., Kawano, H., Goya, T., Tsubouchi, H., Koono, M., and Wakisaka, S. Up-regulation of vascular endothelial growth factor induced by hepatocyte growth factor/scatter factor stimulation in human glioma cells. Biochem. Biophys. Res. Commun. 249: 73-77, 1998.
53. Tomita, N., Morishita, R., Taniyama, Y., Koike, H., Aoki, M., Shimizu, H., Matsumoto, K., Nakamura, T., Kaneda, Y., and Ogihara, T. Angiogenic property of hepatocyte growth factor is dependent on upregulation of essential transcription factor for angiogenesis, ets-1. Circulation, 107: 1411-1417, 2003.
54. Horiguchi, N., Takayama, H., Toyoda, M., Otsuka, T., Fukusato, T., Merlino, G., Takagi, H., and Mori, M. Hepatocyte growth factor promotes hepatocarcinogenesis through c-Met autocrine activation and enhanced angiogenesis in transgenic mice treated with diethylnitrosamine. Oncogene, 21: 1791-1799, 2002.
55. Gmyrek, G. A., Walburg, M., Webb, C. P., Yu, H. M., You, X., Vaughan, E. D., Vande Woude, G. F., and Knudsen, B. S. Normal and malignant prostate epithelial cells differ in their response to hepatocyte growth factor/scatter factor. Am. J. Pathol., 159: 579-590, 2001.
56. Pisters, L. L., Troncoso, P., Zhau, H. E., Li, W., von Eschenbach, A. C., and Chung, L. W. c-met proto-oncogene expression in benign and malignant human prostate tissues. J. Urol., 154: 293-298, 1995.
57. Knudsen, B. S., Gmyrek, G. A., Inra, J., Scherr, D. S., Vaughan, E. D., Nanus, D. M., Kattan, M. W., Gerald, W. L., and Vande Woude, G. F. High expression of the Met receptor in prostate cancer metastasis to bone. Urology, 60: 1113-1117, 2002.
58. Humphrey, P. A., Zhu, X., Zarnegar, R., Swanson, P. E., Ratliff, T. L., Vollmer, R. T., and Day, M. L. Hepatocyte growth factor and its receptor (c-MET) in prostatic carcinoma. Am. J. Pathol., 147: 386-396, 1995.
59. Nishimura, K., Kitamura, M., Takada, S., Nonomura, N., Tsujimura, A., Matsumiya, K., Miki, T., Matsumoto, K., and Okuyama, A. Regulation of invasive potential of human prostate cancer cell lines by hepatocyte growth factor. Int. J. Urol., 5: 276-281, 1998.
60. Qadan, L. R., Perez-Stable, C. M., Schwall, R. H., Burnstein, K. L., Ostenson, R. C., Howard, G. A., and Roos, B. A. Hepatocyte growth factor and vitamin D cooperatively inhibit androgen-unresponsive prostate cancer cell lines. Endocrinology, 141: 2567-2573, 2000.
61. Lara, P. N., Jr., and Meyers, F. J. Treatment options in androgen-independent prostate cancer. Cancer Investig., 17: 137-144, 1999.
62. Papatsoris, A. G., and Papavassiliou, A. G. Prostate cancer: horizons in the development of novel anti-cancer strategies. Curr. Med. Chem. Anti-Cancer Agents, 1: 47-70, 2001.
63. Kurimoto, S., Moriyama, N., Horie, S., Sakai, M., Kameyama, S., Akimoto, Y., Hirano, H., and Kawabe, K. Coexpression of hepatocyte growth factor and its receptor in human prostate cancer. Histochem. J., 30: 27-32, 1998.
64. Hay, R., Cao, B., Skinner, R., Wang, L., Su, Y., Resau, J., Knudsen, B., Gustafson, M., Koo, H-M., Vande Woude, G. F., and and Gross, M. Radioimmunoscintigraphy of human Met-expressing tumor xenografts using Met3, a new monoclonal antibody. Clin. Cancer Res., in press, 2003.
65. Wang, R., Kobayashi, R., and Bishop, J. M. Cellular adherence elicits ligand-independent activation of the Met cell-surface receptor. Proc. Natl. Acad. Sci. USA, 93: 8425-8430, 1996.
66. van Leenders, G., van Balken, B., Aalders, T., Hulsbergen-van de Kaa, C., Ruiter, D., and Schalken, J. Intermediate cells in normal and malignant prostate epithelium express c-MET: implications for prostate cancer invasion. Prostate, 51: 98-107, 2002.
67. Tam, N. N., Chung, S. S., Lee, D. T., and Wong, Y. C. Aberrant expression of hepatocyte growth factor and its receptor, c-Met, during sex hormone-induced prostatic carcinogenesis in the Noble rat. Carcinogenesis (Lond.), 21: 2183-2191, 2000.
68. Jiang, W. G., Grimshaw, D., Lane, J., Martin, T. A., Abounader, R., Laterra, J., Mansel, R. E., and Abounder, R. A hammerhead ribozyme suppresses expression of hepatocyte growth factor/scatter factor receptor c-MET and reduces migration and invasiveness of breast cancer cells. Clin. Cancer Res., 7: 2555-2562, 2001.
69. Herynk, M. H., Stoeltzing, O., Reinmuth, N., Parikh, N. U., Abounader, R., Laterra, J., Radinsky, R., Ellis, L. M., and Gallick, G. E. Down-regulation of c-Met inhibits growth in the liver of human colorectal carcinoma cells. Cancer Res., 63: 2990-2996, 2003.
70. Abounader, R., Lal, B., Luddy, C., Koe, G., Davidson, B., Rosen, E. M., and Laterra, J. In vivo targeting of SF/HGF and c-met expression via UlsnRNA/ribozymes inhibits glioma growth and angiogenesis and promotes apoptosis. FASEB J., 16: 108-110, 2002.
71. Furge, K. A., Kiewlich, D., Le, P., Vo, M. N., Faure, M., Howlett, A. R., Lipson, K. E., Woude, G. F., and Webb, C. P. Suppression of Ras-mediated tumorigenicity and metastasis through inhibition of the Met receptor tyrosine kinase. Proc. Natl. Acad. Sci. USA, 98: 10722-10727, 2001.
72. Firon, M., Shaharabany, M., Altstock, R. T., Horev, J., Abramovici, A., Resau, J. H., Vande Woude, G. F., and Tsarfaty, I. Dominant negative Met reduces tumorigenicity-metastasis and increases tubule formation in mammary cells. Oncogene, 19: 2386-2397, 2000.
73. Cao, B., Su, Y., Oskarsson, M., Zhao, P., Kort, E. J., Fisher, R. J., Wang, L. M., and Vande Woude, G. F. Neutralizing monoclonal antibodies to hepatocyte growth factor/scatter factor (HGF/SF) display antitumor activity in animal models. Proc. Natl. Acad. Sci. USA, 98: 7443-7448, 2001.
74. Maemondo, M., Narumi, K., Saijo, Y., Usui, K., Tahara, M., Tazawa, R., Hagiwara, K., Matsumoto, K., Nakamura, T., and Nukiwa, T. Targeting angiogenesis and HGF function using an adenoviral vector expressing the HGF antagonist NK4 for cancer therapy. Mol. Ther., 5: 177-185, 2002.
75. Matsumoto, K., and Nakamura, T. NK4 (HGF-antagonist/angiogenesis inhibitor) in cancer biology and therapeutics. Cancer Sci., 94: 321-327, 2003.
76. Tomioka, D., Maehara, N., Kuba, K., Mizumoto, K., Tanaka, M., Matsumoto, K., and Nakamura, T. Inhibition of growth, invasion, and metastasis of human pancreatic carcinoma cells by NK4 in an orthotopic mouse model. Cancer Res., 61: 7518-7524, 2001.
77. Davies, G., Mason, M. D., Martin, T. A., Parr, C., Watkins, G., Lane, J., Matsumoto, K., Nakamura, T., and Jiang, W. G. The HGF/SF antagonist NK4 reverses fibroblast- and HGF-induced prostate tumor growth and angiogenesis in vivo. Int. J. Cancer, 106: 348-354, 2003.
78. Lin, S. L., Sukasweang, S., Chuong, C. M., Rasheed, S., and Ying, S. Y. D-RNAi (messenger RNA-antisense DNA interference) as a novel defense system against cancer and viral infections. Curr. Cancer Drug Targets, 1: 241-247, 2001.
79. Webb, C. P., Hose, C. D., Koochekpour, S., Jeffers, M., Oskarsson, M., Sausville, E., Monks, A., and Vande Woude, G. F. The geldanamycins are potent inhibitors of the hepatocyte growth factor/scatter factor-met-urokinase plasminogen activator-plasmin proteolytic network. Cancer Res., 60: 342-349, 2000.
80. Maulik, G., Kijima, T., Ma, P. C., Ghosh, S. K., Lin, J., Shapiro, G. I., Schaefer, E., Tibaldi, E., Johnson, B. E., and Salgia, R. Modulation of the c-Met/hepatocyte growth factor pathway in small cell lung cancer. Clin. Cancer Res., 8: 620-627, 2002.