Gamma secretase inhibition promotes hypoxic necrosis in mouse pancreatic ductal adenocarcinoma

Journal of Experimental Medicine

Volumn 209, Issue 3, 2012, Pages 437-444

  Cook, Natalie ^a,b   Frese, Kristopher K ^a   Bapiro, Tashinga E ^a,b   Jacobetz, Michael A ^a   Gopinathan, Aarthi ^a,b   Miller, Jodi L ^a   Rao, Sudhir S ^c   Demuth, Tim ^c   Howat, William J ^a   Jodrell, Duncan I ^a,b   Tuveson, David A ^a,b  

^a CANCER RESEARCH UK CAMBRIDGE RESEARCH INSTITUTE   (United Kingdom)

^b CAMBRIDGE UNIVERSITY HOSPITALS NHS FOUNDATION TRUST   (United Kingdom)

^c MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GAMMA SECRETASE; GAMMA SECRETASE INHIBITOR; GEMCITABINE; MESSENGER RNA; MRK 003; NOTCH3 RECEPTOR; SURVIVIN; UNCLASSIFIED DRUG;

ADVANCED CANCER; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; CANCER COMBINATION CHEMOTHERAPY; CANCER SURVIVAL; CONTROLLED STUDY; DRUG EFFICACY; ENZYME INHIBITION; HYPOXIA; KIDNEY; LETTER; LIVER; MONOTHERAPY; MOUSE; NONHUMAN; PANCREAS ADENOCARCINOMA; PRIORITY JOURNAL; SPLEEN; TUMOR MICROENVIRONMENT;

AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; ANOXIA; CARCINOMA, PANCREATIC DUCTAL; CELL LINE, TUMOR; CELL PROLIFERATION; CYCLIC S-OXIDES; DEOXYCYTIDINE; DRUG SYNERGISM; DRUG THERAPY, COMBINATION; ENDOTHELIAL CELLS; HUMANS; MICE; MICE, MUTANT STRAINS; NECROSIS; PANCREATIC NEOPLASMS; PROTEASE INHIBITORS; RECEPTORS, NOTCH; SIGNAL TRANSDUCTION; THIADIAZOLES; TRANSLATIONAL MEDICAL RESEARCH;

EID: 84860374357     PISSN: 00221007     EISSN: 15409538     Source Type: Journal    
DOI: 10.1084/jem.20111923     Document Type: Letter

References (36)

1. Bapiro, T.E., F.M. Richards, M.A. Goldgraben, K.P. Olive, B. Madhu, K.K. Frese, N. Cook, M.A. Jacobetz, D.M. Smith, D.A. Tuveson, et al. 2011. A novel method for quantification of gemcitabine and its metabolites 2-,2-difluorodeoxyuridine and gemcitabine triphosphate in tumour tissue by LC-MS/MS: comparison with (19)F NMR spectroscopy. Cancer Chemother. Pharmacol. 68:1243-1253. http://dx.doi.org/10.1007/s00280-011-1613-0
2. Beatty, G.L., E.G. Chiorean, M.P. Fishman, B. Saboury, U.R. Teitelbaum, W. Sun, R.D. Huhn, W. Song, D. Li, L.L. Sharp, et al. 2011. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science. 331:1612-1616. http://dx.doi.org/10.1126/science.1198443
3. Bray, S., and F. Bernard. 2010. Notch targets and their regulation. Curr. Top. Dev. Biol. 92:253-275. http://dx.doi.org/10.1016/S0070-2153(10)92008-5
4. Burris, H.A. III, M.J. Moore, J. Andersen, M.R. Green, M.L. Rothenberg, M.R. Modiano, M.C. Cripps, R.K. Portenoy, A.M. Storniolo, P. Tarassoff, et al. 1997. 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.
5. Chen, Y.Q., C.L. Zhao, and W. Li. 2009. Effect of hypoxia-inducible factor-1alpha on transcription of survivin in non-small cell lung cancer. J. Exp. Clin. Cancer Res. 28:29. http://dx.doi.org/10.1186/1756-9966-28-29
6. Fitzgerald, K., A. Harrington, and P. Leder. 2000. Ras pathway signals are required for notch-mediated oncogenesis. Oncogene. 19:4191-4198. http://dx.doi.org/10.1038/sj.onc.1203766
7. Gustafsson, M.V., X. Zheng, T. Pereira, K. Gradin, S. Jin, J. Lundkvist, J.L. Ruas, L. Poellinger, U. Lendahl, and M. Bondesson. 2005. Hypoxia requires notch signaling to maintain the undifferentiated cell state. Dev. Cell. 9:617-628. http://dx.doi.org/10.1016/j.devcel.2005.09.010
8. Hanlon, L., J.L. Avila, R.M. Demarest, S. Troutman, M. Allen, F. Ratti, A.K. Rustgi, B.Z. Stanger, F. Radtke, V. Adsay, et al. 2010. Notch1 functions as a tumor suppressor in a model of K-ras-induced pancreatic ductal adenocarcinoma. Cancer Res. 70:4280-4286. http://dx.doi.org/10.1158/0008-5472.CAN-09-4645
9. Hezel, A.F., A.C. Kimmelman, B.Z. Stanger, N. Bardeesy, and R.A. Depinho. 2006. Genetics and biology of pancreatic ductal adenocarcinoma. Genes Dev. 20:1218-1249. http://dx.doi.org/10.1101/gad.1415606
10. Hingorani, S.R., E.F. Petricoin, A. Maitra, V. Rajapakse, C. King, M.A. Jacobetz, S. Ross, T.P. Conrads, T.D. Veenstra, B.A. Hitt, et al. 2003. Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell. 4:437-450. http://dx.doi.org/10.1016/S1535-6108(03)00309-X
11. Hingorani, S.R., L. Wang, A.S. Multani, C. Combs, T.B. Deramaudt, R.H. Hruban, A.K. Rustgi, S. Chang, and D.A. Tuveson. 2005. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell. 7:469-483. http://dx.doi.org/10.1016/j.ccr.2005.04.023
12. Indraccolo, S., S. Minuzzo, M. Masiero, I. Pusceddu, L. Persano, L. Moserle, A. Reboldi, E. Favaro, M. Mecarozzi, G. Di Mario, et al. 2009. Crosstalk between tumor and endothelial cells involving the Notch3-Dll4 interaction marks escape from tumor dormancy. Cancer Res. 69:1314-1323. http://dx.doi.org/10.1158/0008-5472.CAN-08-2791
13. Jones, S., X. Zhang, D.W. Parsons, J.C. Lin, R.J. Leary, P. Angenendt, P. Mankoo, H. Carter, H. Kamiyama, A. Jimeno, et al. 2008. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 321:1801-1806. http://dx.doi.org/10.1126/science.1164368
14. Jorissen, E., and B. De Strooper. 2010. Gamma-secretase and the intramembrane proteolysis of Notch. Curr. Top. Dev. Biol. 92:201-230. http://dx.doi.org/10.1016/S0070-2153(10)92006-1
15. Kindler, H.L., D. Niedzwiecki, D. Hollis, S. Sutherland, D. Schrag, H. Hurwitz, F. Innocenti, M.F. Mulcahy, E. O-Reilly, T.F. Wozniak, et al. 2010. Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the Cancer and Leukemia Group B (CALGB 80303). J. Clin. Oncol. 28:3617-3622. http://dx.doi.org/10.1200/JCO.2010.28.1386
16. Kopan, R., and M.X. Ilagan. 2004. Gamma-secretase: proteasome of the membrane? Nat. Rev. Mol. Cell Biol. 5:499-504. http://dx.doi.org/10.1038/nrm1406
17. Mazur, P.K., H. Einwächter, M. Lee, B. Sipos, H. Nakhai, R. Rad, U. Zimber-Strobl, L.J. Strobl, F. Radtke, G. Klöppel, et al. 2010. Notch2 is required for progression of pancreatic intraepithelial neoplasia and development of pancreatic ductal adenocarcinoma. Proc. Natl. Acad. Sci. USA. 107:13438-13443. http://dx.doi.org/10.1073/pnas.1002423107
18. Meng, R.D., C.C. Shelton, Y.M. Li, L.X. Qin, D. Notterman, P.B. Paty, and G.K. Schwartz. 2009. gamma-Secretase inhibitors abrogate oxaliplatin-induced activation of the Notch-1 signaling pathway in colon cancer cells resulting in enhanced chemosensitivity. Cancer Res. 69:573-582. http://dx.doi.org/10.1158/0008-5472.CAN-08-2088
19. Mita, A.C., M.M. Mita, S.T. Nawrocki, and F.J. Giles. 2008. Survivin: key regulator of mitosis and apoptosis and novel target for cancer therapeutics. Clin. Cancer Res. 14:5000-5005. http://dx.doi.org/10.1158/1078-0432.CCR-08-0746
20. Miyamoto, Y., A. Maitra, B. Ghosh, U. Zechner, P. Argani, C.A. Iacobuzio-Donahue, V. Sriuranpong, T. Iso, I.M. Meszoely, M.S. Wolfe, et al. 2003. Notch mediates TGF alpha-induced changes in epithelial differentiation during pancreatic tumorigenesis. Cancer Cell. 3:565-576. http://dx.doi.org/10.1016/S1535-6108(03)00140-5
21. Olive, K.P., M.A. Jacobetz, C.J. Davidson, A. Gopinathan, D. McIntyre, D. Honess, B. Madhu, M.A. Goldgraben, M.E. Caldwell, D. Allard, et al. 2009. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science. 324:1457-1461. http://dx.doi.org/10.1126/science.1171362
22. Pannuti, A., K. Foreman, P. Rizzo, C. Osipo, T. Golde, B. Osborne, and L. Miele. 2010. Targeting Notch to target cancer stem cells. Clin. Cancer Res. 16:3141-3152. http://dx.doi.org/10.1158/1078-0432.CCR-09-2823
23. Phng, L.K., and H. Gerhardt. 2009. Angiogenesis: a team effort coordinated by notch. Dev. Cell. 16:196-208. http://dx.doi.org/10.1016/j.devcel.2009.01.015
24. Plentz, R., J.S. Park, A.D. Rhim, D. Abravanel, A.F. Hezel, S.V. Sharma, S. Gurumurthy, V. Deshpande, C. Kenific, J. Settleman, et al. 2009. Inhibition of gamma-secretase activity inhibits tumor progression in a mouse model of pancreatic ductal adenocarcinoma. Gastroenterology. 136:1741-1749: e6. http://dx.doi.org/10.1053/j.gastro.2009.01.008
25. Pradeep, C.R., W.J. Köstler, M. Lauriola, R.Z. Granit, F. Zhang, J. Jacob-Hirsch, G. Rechavi, H.B. Nair, B.T. Hennessy, A.M. Gonzalez-Angulo, et al. 2011. Modeling ductal carcinoma in situ: a HER2-Notch3 collaboration enables luminal filling. Oncogene. In press.
26. Raleigh, J.A., S.C. Chou, L. Tables, S. Suchindran, M.A. Varia, and M.R. Horsman. 1998. Relationship of hypoxia to metallothionein expression in murine tumors. Int. J. Radiat. Oncol. Biol. Phys. 42:727-730. http://dx.doi.org/10.1016/S0360-3016(98)00329-0
27. Sahlgren, C., M.V. Gustafsson, S. Jin, L. Poellinger, and U. Lendahl. 2008. Notch signaling mediates hypoxia-induced tumor cell migration and invasion. Proc. Natl. Acad. Sci. USA. 105:6392-6397. http://dx.doi.org/10.1073/pnas.0802047105
28. Sasai, Y., R. Kageyama, Y. Tagawa, R. Shigemoto, and S. Nakanishi. 1992. Two mammalian helix-loop-helix factors structurally related to Drosophila hairy and Enhancer of split. Genes Dev. 6:2620-2634. http://dx.doi.org/10.1101/gad.6.12b.2620
29. Schreiber, F.S., T.B. Deramaudt, T.B. Brunner, M.I. Boretti, K.J. Gooch, D.A. Stoffers, E.J. Bernhard, and A.K. Rustgi. 2004. Successful growth and characterization of mouse pancreatic ductal cells: functional properties of the Ki-RAS(G12V) oncogene. Gastroenterology. 127:250-260. http://dx.doi.org/10.1053/j.gastro.2004.03.058
30. Simeone, D.M. 2008. Pancreatic cancer stem cells: implications for the treatment of pancreatic cancer. Clin. Cancer Res. 14:5646-5648. http://dx.doi.org/10.1158/1078-0432.CCR-08-0584
31. Singh, M., A. Lima, R. Molina, P. Hamilton, A.C. Clermont, V. Devasthali, J.D. Thompson, J.H. Cheng, H. Bou Reslan, C.C. Ho, et al. 2010. Assessing therapeutic responses in Kras mutant cancers using genetically engineered mouse models. Nat. Biotechnol. 28:585-593. http://dx.doi.org/10.1038/nbt.1640
32. Smit, V.T., A.J. Boot, A.M. Smits, G.J. Fleuren, C.J. Cornelisse, and J.L. Bos. 1988. KRAS codon 12 mutations occur very frequently in pancreatic adenocarcinomas. Nucleic Acids Res. 16:7773-7782. http://dx.doi.org/10.1093/nar/16.16.7773
33. Stanger, B.Z., B. Stiles, G.Y. Lauwers, N. Bardeesy, M. Mendoza, Y. Wang, A. Greenwood, K.H. Cheng, M. McLaughlin, D. Brown, et al. 2005. Pten constrains centroacinar cell expansion and malignant transformation in the pancreas. Cancer Cell. 8:185-195. http://dx.doi.org/10.1016/j.ccr.2005.07.015
34. Stockhausen, M.T., J. Sjölund, C. Manetopoulos, and H. Axelson. 2005. Effects of the histone deacetylase inhibitor valproic acid on Notch signalling in human neuroblastoma cells. Br. J. Cancer. 92:751-759. http://dx.doi.org/10.1038/sj.bjc.6602309
35. Van Cutsem, E., W.L. Vervenne, J. Bennouna, Y. Humblet, S. Gill, J.L. Van Laethem, C. Verslype, W. Scheithauer, A. Shang, J. Cosaert, and M.J. Moore. 2009. Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. J. Clin. Oncol. 27:2231-2237. http://dx.doi.org/10.1200/JCO.2008.20.0238
36. van Es, J.H., M.E. van Gijn, O. Riccio, M. van den Born, M. Vooijs, H. Begthel, M. Cozijnsen, S. Robine, D.J. Winton, F. Radtke, and H. Clevers. 2005. Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. Nature. 435:959-963. http://dx.doi.org/10.1038/nature03659