Blockade of the epidermal growth factor receptor signaling by a novel tyrosine kinase inhibitor leads to apoptosis of endothelial cells and therapy of human pancreatic carcinoma

Cancer Research

Volumn 60, Issue 11, 2000, Pages 2926-2935

  Bruns, Christiane J ^a   Solorzano, Carmen C ^a   Harbison, Matthew T ^a   Ozawa, Shutaro ^a   Tsan, Rachel ^a   Fan, Dominic ^a   Abbruzzese, James ^a   Traxler, Peter ^b   Buchdunger, Elisabeth ^b   Radinsky, Robert ^a   Fidler, Isaiah J ^a  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b NOVARTIS PHARMA AG   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

6 (4 HYDROXYPHENYL) 4 (ALPHA METHYLBENZYLAMINO) 7H PYRROLO[2,3 D]PYRIMIDINE; EPIDERMAL GROWTH FACTOR RECEPTOR; GEMCITABINE; PROTEIN TYROSINE KINASE INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER INHIBITION; CANCER SURVIVAL; CONTROLLED STUDY; DRUG EFFECT; DRUG SCREENING; HUMAN; HUMAN CELL; LIVER METASTASIS; LYMPH NODE METASTASIS; MALE; METASTASIS INHIBITION; MOUSE; NONHUMAN; PANCREAS CARCINOMA; PRIORITY JOURNAL; SIGNAL TRANSDUCTION;

ADMINISTRATION, ORAL; ANIMALS; ANTIGENS, CD31; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; APOPTOSIS; BLOTTING, WESTERN; DEOXYCYTIDINE; DOWN-REGULATION; ENDOTHELIUM; FLUORESCENT ANTIBODY TECHNIQUE; HUMANS; IMMUNOHISTOCHEMISTRY; IN SITU NICK-END LABELING; MALE; MICE; MICE, NUDE; NEOPLASM TRANSPLANTATION; PANCREATIC NEOPLASMS; PROTEIN-TYROSINE KINASES; PYRIMIDINES; PYRROLES; RECEPTOR, EPIDERMAL GROWTH FACTOR; SIGNAL TRANSDUCTION; TIME FACTORS; TUMOR CELLS, CULTURED;

EID: 0034212763     PISSN: 00085472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (75)

1. Warshaw, A. L., and Fernandez-del Castillo, C. Pancreatic carcinoma. N. Engl. J. Med., 326: 455-465, 1992.
2. Evans, D. B., Abbruzzese, J. L., and Rich, T. R. Cancer of the pancreas. In: V. T. de Vita, S. Hellman, and S. A. Rosenberg (eds.), Cancer: Principles and Practice of Oncology, Ed. 5, pp. 1054-1087. Philadelphia: J. B. Lippincott, 1997.
3. Wanebo, H. J., and Vezeridis, M. P. Pancreatic carcinoma in perspective: a continuing challenge. Cancer (Phila.), 78: 580-591, 1996.
4. Landis, S. H., Murray, T., Bolden, S., and Wingo, P. A. Cancer statistics, 1999. CA Cancer J. Clin., 49: 8-31, 1999.
5. Fernandez, E., La Vecchia, C., Porta, M., Negri, E., Lucchini, F., and Levi F. Trends in pancreatic cancer mortality in Europe, 1955-1989. Int. J. Cancer, 57: 786-792, 1994.
6. Burris, H. A., III, Moore, M. J., Andersen, J., Green, M. R., and Rothenberg, M. L. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J. Clin. Oncol., 15: 2403-2413, 1997.
7. Almoguera, C., Shibata, D., Forrester, K., Martin, J., Arnheim, N., and Perucho, M. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell, 53: 549-554, 1988.
8. Pellegata, N., Sessa, F., Renault, B., Bonto, M., Leone, B., Solicia, E., and Ranzani, G. K-ras and p53 gene mutations in pancreatic cancer: ductal and nonductal tumors progress through different genetic lesions. Cancer Res., 54: 1556-1560, 1994.
9. Caldas, C., Hahn, S., da Costa, L., Redston, M., Schutte, M., Seymour, A., Weinstein, C., Hruban, R., Yeo, C., and Kern, S. Frequent somatic mutations and homozygous deletions of the p16 (MTSI) gene in pancreatic adenocarcinoma. Nat. Genet., 8: 27-32, 1994.
10. Hahn, S. A., Schutte, M., Hoque, A. T., Moskaluk, C. A., da Costa, L. T., Rozenblum, E., Weinstein, C. L., Fisher, A., Yeo, C. J., Hruban, R. H., and Kern, S. E. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science (Washington DC), 271: 350-353, 1996.
11. waf1 expression and growth inhibition by transforming growth factor-β is mediated by the tumor suppressor gene DPC-4 in human pancreatic adenocarcinoma cells. Cancer Res., 57: 3929-3934, 1997.
12. Sinicrope, F. A., Evans, D. B., Leach, S. D., Cleary, K. R., Fenoglio, C. J., Lee, J. J., and Abbruzzese, J. L. Bcl-2 and p53 expression in resectable pancreatic adenocarcinomas-association with clinical outcome. Clin. Cancer Res., 2: 2015-2022, 1996.
13. Korc, M., Chandrasekar, B., Yamanaka, Y., Friess, H., Buchier, M., and Beger, H. G. Overexpression of the epidermal growth factor receptor in human pancreatic cancer is associated with concomitant increases in the levels of epidermal growth factor and transforming growth factor α. J. Clin. Investig., 90: 1352-1360, 1993.
14. Yamanaka, Y., Friess, H., Kobrin, M. S., Buchler, M., Kunz, J., Beger, H. G., and Korc, M. Overexpression of HER2/neu oncogene in human pancreatic carcinoma. Hum. Pathol., 24: 1127-1134, 1993.
15. Bergmann, U., Funatomi, H., Yokoyama, M., Beger, H. G., and Korc, M. Insulin-like growth factor 1 overexpression in human pancreatic cancer: evidence for autocrine and paracrine roles. Cancer Res., 55: 2007-2011, 1995.
16. Wagner, M., Lopez, M. E., Cahn, M., and Korc, M. Suppression of fibroblast growth factor receptor signaling inhibits pancreatic cancer growth in vitro and in vivo. Gastroenterology. 114: 798-807, 1998.
17. Smith, J. J., Derynck, R., and Korc, M. Production of transforming growth factor α in human pancreatic cancer cells: evidence for a superagonist autocrine cycle. Proc. Natl. Acad. Sci. USA, 84: 7567-7570, 1987.
18. Ebert, M., Yokoyama, M., Kobrin, M. S., Friess, H., Lopez, M. E., Buchler, M. W., Johnson, G. R., and Korc, M. Induction and expression of amphiregulin in human pancreatic cancer. Cancer Res., 54: 3959-3962, 1994.
19. Kobrin, M. S., Funatomi, H., Friess, H., Buchler, M. W., Stathis, P., and Korc, M. Induction and expression of heparin-binding EGF-like growth factor in human pancreatic cancer. Biochem. Biophys. Res. Commun., 202: 1705-1709, 1994.
20. Yamanaka, Y., Friess, H., Kobrin, M. S., Buchler, M., Beger, H. G., and Korc, M. Coexpression of epidermal growth factor receptor and ligands in human pancreatic cancer is associated with enhanced tumor aggressiveness. Anticancer Res., 13: 565-569, 1993.
21. Wagner, M., Cao, T., Lopez, M. E., Hope, C., van Nostrand, K., Kobrin, M. S., Fan, H. U., Buchler, M. W., and Korc, M. Expression of a truncated EGF receptor is associated with inhibition of pancreatic cancer cell growth and enhanced sensitivity to cisplatinum. Int. J. Cancer. 68: 782-787, 1996.
22. Folkman, J. Angiogenesis in cancer, vascular, rheumatoid and other diseases. Nat. Med., 1: 27-31, 1995.
23. Hanahan, D., and Folkman, J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell, 86: 353-364, 1996.
24. Bruns, C. J., Harbison, M. T., Kuniyasu, H., Eue, I., and Fidler, I. J. In vivo selection and characterization of metastatic variants from human pancreatic adenocarcinoma by using orthotopic implantation in nude mice. Neoplasia, 1: 50-62, 1999.
25. Kuniyasu, H., Ellis, L. M., Evans, D. B., Ahbruzzese, J. L., Fenoglio, C. J., Bucana, C. D., Cleary, K. R., Tahara, E., and Fidler, I. J. Relative expression of E-cadherin and type IV collagenase genes predicts disease outcome in patients with resectable pancreatic carcinoma. Clin. Cancer Res., 5: 25-33, 1999.
26. Ferrara, N. The role of vascular endothelial growth factor in pathological angiogenesis. Breast Cancer Res. Treat., 36: 127-137, 1995.
27. Goldman, C. K., Kim, J., Wong, W. L., King, V., Brock, T., and Gillespie, G. Y. Epidermal growth factor stimulates vascular endothelial growth factor production by human malignant glioma cells: a model of glioblastoma multiforme pathophysiology. Mol. Biol. Cell, 4: 121-133, 1993.
28. Schreiber, A. B., Winkler, M. E., and Derynck, R. Transforming growth factor-α: a more potent angiogenic mediator than epidermal growth factor. Science (Washington DC), 232: 1250-1253, 1986.
29. Petit, A. M., Rak, J., Hung, M. C., Rockwell, P., Goldstein, N., Fendly, B., and Kerbel, R. S. Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solid tumors. Am. J. Pathol., 151: 1523-1530, 1997.
30. Rak, J., Filmus, J., and Kerbel, R. S. Reciprocal paracrine interactions between tumour cells and endothelial cells: the "angiogenesis progression" hypothesis. Eur. J. Cancer, 32A: 2438-2450, 1996.
31. Perrotte, P., Matsumoto, T., Inoue, K., Kuniyasu, H., Eve, B. Y., Hicklin, D. J., Radinsky, R., and Dinney, C. P. Antiepidermal growth factor receptor antibody C225 inhibits angiogenesis in human transitional cell carcinoma growing orthotopically in nude mice. Clin. Cancer Res., 5: 257-265, 1999.
32. Morgan, R. T., Woods, L. K., Moore, G. E., Quinn, L. A., McGavran, L., and Gordon, S. G. Human cell line (COLO375) of metastatic pancreatic adenocarcinoma. Int. J. Cancer, 25: 591-598, 1980.
33. Vezeridis, M. P., Tzanakakis, G. N., Meitner, P. A., Doremus, C. M., and Tibbetts, L. M. In vivo selection of a highly metastatic cell line of a human pancreatic carcinoma in the nude mouse. Cancer (Phila.), 69: 2060-2963, 1992.
34. Traxler, P., Buchdunger, E., Furet, P., Gschwind, H-P., Ho, P., Mett, H., O'Reilly, T., Pfaar, U., and Thomas, H. Preclinical profile of PKI166-a novel and potent EGF-R tyrosine kinase inhibitor for clinical development (abstr.) Clin. Cancer Res., 5: 3750s, 1999.
35. McGlynn, E., Becker, M., Mett, H., Reutener, S., Cozens, R., and Lydon, N. B. Large scale purification and characterization of a recombinant epidermal growth factor receptor protein-tyrosine kinase. Eur. J. Biochem., 207, 265-275, 1992.
36. Geissler, J. F., Roesel, J. L., Meyer, T., Trinks, U. P., Traxler, P., and Lydon, N. B. Benzopyranones and benzothiopyranones: a class of tyrosine protein kinase inhibitors with selectivity for the v-Abl kinase. Cancer Res., 52: 4492-4498, 1992.
37. Geissler, J. F., Traxler, P., Regenass, U., Murray, B. J., Roesel, J. L., Meyer, T., McGlynn, E., Storni, A., and Lydon, N. B. Thiazolidine-diones. Biochemical and biological activity of a novel class of tyrosine protein kinase inhibitors. J. Biol. Chem., 265: 22255-22261, 1990.
38. Bhat, A., Kolibaba, K. S., Oda, T., Ohno-Jones, S., and Druker, B. J. Interactions of CBL with BCR-ABL and CRKL in BCR-ABL-transformed myeloid cells. J. Biol. Chem., 272: 16170-16175, 1997.
39. Arion, D., Meijer, L., and Beach, D. Cdc-2 is a component of the M-phase specific histone H1 kinase: evidence for identity with MPF. Cell, 55: 371-378, 1988.
40. Partanen, J., Armstrong, E., Bergman, M., Makela, T. P., Hirvonen, H., Huebner, K., and Alitalo, K. Cyl encodes a putative cytoplasmic tyrosine kinase lacking the conserved tyrosine autophosphorylation site (Y416 src). Oncogene, 6: 2013-2018, 1991.
41. McGlynn, E., Liebetanz, J., Reutener, S., Wood, J., Lydon, N. B., Hofstetter, H., Vanek, M., Meyer, T., and Fabbro, D. Expression and partial characterization of rat protein kinase C and protein kinase C in insert cells using recombinant baculovirus. J. Cell. Biochem., 49: 239-250, 1992.
42. Shi, S. R., Key, M. E., and Kalra, K. L. Antigen retrieval in formalin-fixed, paraffin-embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. J. Histochem. Cytochem., 39: 741-748, 1991.
43. Weidner, N., Semple, J. P., Welch, W. R., and Folkman, J. Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma. N. Engl. J. Med., 324: 1-8, 1991.
44. Yoneda, J., Kuniyasu, H., Crispens, M. A., Price, J. E., Bucana, C. D., and Fidler, I. J. Expression of angiogenesis-related genes and progression of human ovarian carcinomas in nude mice. J. Natl. Cancer Inst., 90: 447-454, 1998.
45. Radinsky, R., Risin, S., Fan, D., Dong, Z., Bielenberg, D., Bucana, C, D., and Fidler, I. J. Level and function of epidermal growth factor receptor predict the metastatic potential of human colon carcinoma cells. Clin. Cancer Res., 1: 19-31, 1995.
46. Fan, D., Poste, G., O'Brian, C. A., Seid, C., Ward, N. E., Earnest, L. E., and Fidler, I. J. Chemosensitization of murine fibrosarcoma cells to drugs affected by the multidrug resistance phenotype by the antidepressant trazodone: an experimental model for the reversal of intrinsic drug resistance. Int. J. Oncol., 1: 735-742, 1992.
47. Parker, C., Roseman, B. J., Bucana, C. D., Tsan, R., and Radinsky, R. Preferential activation of the epidermal growth factor receptor in human colon carcinoma liver metastases in nude mice. J. Histochem. Cytochem., 46: 595-602, 1998.
48. Ullrich, A., Coussens, L., Hayflick, J. S., Dull, T. J., Gray, A., Tam, A. W., Lee, J., Yarden, Y., Libermann, T. A., and Schlessinger, J. Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. Nature (Lond.), 309: 418-425, 1984.
49. Massagué, J., and Pandiella, A. Membrane-anchored growth factors. Annu. Rev. Biochem., 62: 515-541, 1993.
50. Pazin, M. J., and Williams, L. T. Triggering signaling cascades by receptor tyrosine kinases. Trends Biochem. Sci., 17: 374-378, 1992.
51. Uckun, F. M., Narla, R. K., Jun, X., Zeren, T., Venkatachalam, T., Waddick, K. G., Rostostev, A., and Myers, D. E. Cytotoxic activity of epidermal growth factor-Genistein against breast cancer cells. Clin. Cancer Res., 4: 901-912, 1998.
52. Uckun, F. M., Narla, R. K., Zeren, T., Yanishevski, Y., Myers, D. E., Waurzyniak, B., Ek, O., Schneider, E., Messinger, Y., Chelstrom, L. M., Gunther, R., and Evans, W. In vivo toxicity, pharmacokinetics, and anticancer activity of Genistein linked to recombinant human epidermal growth factor. Clin. Cancer Res., 4: 1125-1134, 1998.
53. Mendelsohn, J. Epidermal growth factor receptor inhibition by a monoclonal antibody as anticancer therapy. Clin. Cancer Res., 3: 2703-2707, 1997.
54. Lipson, K. E., Pang, L., Huber, L. J., Chen, H., Tsai, J. M., Hirth, P., Gazit, A., Levitzki, A., and McMahon, G. Inhibition of platelet-derived growth factor and epidermal growth factor receptor signaling events after treatment of cells with specific synthetic inhibitors of tyrosine kinase phosphorylation. J. Pharmacol. Exp. Ther., 285; 844-852, 1998.
55. Ciardiello, F., Damiano, V., Bianco, R., Bianco, C., Fontanini, C., De Laurentiis, M., De Placido, S., Mendelsohn, J., Bianco, A. R., and Tortora, G. Antitumor activity of combined blockade of epidermal growth factor receptor and protein kinase A. J. Natl. Cancer Inst., 88: 1770-1776, 1996.
56. Huang, S. M., Bock, J. M., and Harari, P. M. Epidermal growth factor receptor blockade with C225 modulates proliferation, apoptosis, and radiosensitivity in squamous cell carcinomas of the head and neck. Cancer Res., 59: 1935-1940, 1999.
57. Baselga, J., Norton, L., Masui, H., Pandiella, A., Coplan, K., Miller, W. H. J., and Mendelsohn, J. Antitumor effects of doxorubicin in combination with anti-epidermal growth factor receptor monoclonal antibodies. J. Natl. Cancer Inst., 85: 1327-1333, 1993.
58. van Gog, F. B., Brakenhoff, R. H., and Stigter-van Snow, G. B. Perspectives of combined radioimmunotherapy and anti-EGFR antibody therapy for the treatment of residual head and neck cancer. Int. J. Cancer, 77: 13-18, 1998.
59. Aboud-Pirak, E., Hurwitz, E., Pirak, M. E., Bellot, F., Schlessinger, J., and Sela, M. Efficacy of antibodies to epidermal growth factor receptor against KB carcinoma in vitro and in nude mice. J. Natl. Cancer Inst., 80: 1605-1611, 1988.
60. Shiurba, R. A., Eng, L. F., Vogel, H., Lee, Y. L., Horoupian, D. S., and Urich, H. Epidermal growth factor receptor in meningiomas is expressed predominantly on endothelial cells. Cancer (Phila.), 62: 2139-2144, 1988.
61. Bohling, T., Hatva, E., Kujala, M., Claesson-Welsh, L., Alitalo, K., and Haltia, M. Expression of growth factors and growth factor receptors in capillary hemangioblastoma. J. Neuropathol. Exp. Neurol., 55: 522-527, 1996.
62. Rockwell, P., O'Connor, W. J., King, K., Goldstein, N. I., Zhang, L. M., and Stein, C. A. Cell-surface perturbations of the epidermal growth factor and vascular endothelial growth factor receptors by phosphorothioate oligodeoxynucleotides. Proc. Natl. Acad. Sci. USA, 94: 6523-6528, 1997.
63. Benjamin, L. E., Golijanin, D., Itin, A., Pode, D., and Keshet, E. Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal. J. Clin. Investig., 103: 159-165, 1999.
64. Benjamin, L. E., and Keshet, E. Conditioned switching of vascular endothelial growth factor (VEGF) expression in tumors: induction of endothelial cell shedding and regression of hemangioblastoma-like vessels by VEGF withdrawal. Proc. Natl. Acad. Sci. USA, 94: 8761-8766, 1997.
65. Kumar, R., Yoneda, J., Bucana, C. D., and Fidler, I. J. Regulation of distinct steps of angiogenesis by different angiogenic molecules. Int. J. Oncol., 12: 749-757, 1998.
66. Kitadai, Y., Haruma, K., Sumii, K., Yamamoto, S., Ue, T., Yokozaki, H., Yasui, W., Ohmoto, Y., Fidler, I. J., Tahara, E., and Kajiyama, G. Expression of interleukin-8 correlates with vascularity in human gastric carcinomas. Am. J. Pathol. 152: 93-100, 1998.
67. Xu, L., Xie, K., Mukaida, N., Matsushima, K., and Fidler, I. J. Hypoxia-induced elevation in interleukin-8 expression by human ovarian carcinoma cells. Cancer Res., 59: 5822-5829, 1999.
68. Syridopoulos, I., Brogi, E., Kearney, M., Sullivan, A. B., Cetrulo, C., Isner, M., and Losordo, D. W. Vascular endothelial growth factor inhibits endothelial cell apoptosis induced by tumor necrosis factor-alpha: balance between growth and death signals. J. Mol. Cell Cardiol., 29: 1321-1330, 1997.
69. Gerber, H. P., Dixit, V., and Ferrara, N. Vascular endothelial growth factor induces expression of the antiapoptotic proteins Bcl-2 and A1 in vascular endothelial cells. J. Biol. Chem., 273: 13313-13316, 1998.
70. Nor, J. E., Christensen, J., Mooney, D. J., and Polverini, P. J. Vascular endothelial growth factor (VEGF)-mediated angiogenesis is associated with enhanced endothelial cell survival and induction of Bcl-2 expression. Am. J. Pathol., 154: 375-384, 1999.
71. Watanabe, Y., and Dvorak, H. V. Vascular permeability factor/vascular endothelial growth factor inhibits anchorage-disruption-induced apoptosis in microvessel endothelial cells by inducing scaffold formation. Exp. Cell Res., 233: 340-349, 1997.
72. Kerbel, R. S., Viloria-Petit, A., Okada, F., and Rak, J. Establishing a link between oncogenes and tumor angiogenesis. Mol. Med., 4: 286-295, 1998.
73. Grugel, S., Finkenzeller, G., Weindel, K., Barleon, B., and Marme, D. Both v-Ha-Ras and v-Raf stimulate expression of the vascular endothelial growth factor in NIH 3T3 cells. J. Biol. Chem., 270: 25915-25919, 1995.
74. Rozakis-Adcock, M., Fernley, R., Wade, J., Pawson, T., and Bowtell, D. The SH2 and SH3 domains of mammalian Grb2 couple the EGF receptor to the Ras activator mSosl. Nature (Lond.), 363: 83-85, 1993.
75. Rak, J., Mitsuhashi, Y., Bayko, L., Filmus, J., Shirasawa, S., Sasazuki, T., and Kerbel, R. S. Mutant ras oncogene upregulates VEGF/VPF expression: implications for induction and inhibition of tumor angiogenesis. Cancer Res., 55: 4575-4580, 1995.