Stem cells as the root of pancreatic ductal adenocarcinoma

Experimental Cell Research

Volumn 318, Issue 6, 2012, Pages 691-704

  Balic, Anamaria ^a   Dorado, Jorge ^a   Alonso Gómez, Mercedes ^a   Heeschen, Christopher ^a  

^a Structural Biology and Biocomputing Programme   (Spain)

Author keywords

Cancer stem cells; Inflammation; Pancreatic cancer; Targeted therapy; Tumor initiating cells

Indexed keywords

BONE MORPHOGENETIC PROTEIN 2; CD133 ANTIGEN; CD24 ANTIGEN; CHEMOKINE RECEPTOR CCR7; CHEMOKINE RECEPTOR CXCR4; CURCUMIN; EPITHELIAL CELL ADHESION MOLECULE; GEMCITABINE; HERMES ANTIGEN; HYPOXIA INDUCIBLE FACTOR 1ALPHA; IMETELSTAT; INSULIN; MAMMALIAN TARGET OF RAPAMYCIN; MULTIDRUG RESISTANCE PROTEIN 5; NEUROGENIN 3; NOTCH RECEPTOR; PANCREATIC ELASTASE; PHOSPHATIDYLINOSITOL 3 KINASE; RAPAMYCIN; STROMAL CELL DERIVED FACTOR 1; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR HES 1; TRANSCRIPTION FACTOR PAX4; TRANSCRIPTION FACTOR PDX 1; VASCULOTROPIN; WNT PROTEIN;

ACINAR CELL; CANCER GROWTH; CANCER RELAPSE; CANCER RESISTANCE; CANCER STEM CELL; CARCINOGENESIS; CELL ISOLATION; CHRONIC PANCREATITIS; HUMAN; INFLAMMATION; METASTASIS; PANCREAS ADENOCARCINOMA; PANCREAS ISLET ALPHA CELL; PANCREAS ISLET BETA CELL; PANCREATIC DUCTAL ADENOCARCINOMA; PRIORITY JOURNAL; PROGENY; PROTEIN EXPRESSION; RADIOSENSITIVITY; REVIEW; SIGNAL TRANSDUCTION; STEM CELL;

EID: 84857653680     PISSN: 00144827     EISSN: 10902422     Source Type: Journal    
DOI: 10.1016/j.yexcr.2011.11.007     Document Type: Review

References (108)

1. Burris H.A., Moore M.J., Andersen J., Green M.R., Rothenberg M.L., Modiano M.R., Cripps M.C., Portenoy R.K., Storniolo A.M., Tarassoff P., Nelson R., Dorr F.A., Stephens C.D., Von Hoff D.D. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J. Clin. Oncol. 1997, 15:2403-2413.
2. Ahlgren J.D. Chemotherapy for pancreatic carcinoma. Cancer 1996, 78:654-663.
3. Jemal A., Siegel R., Xu J., Ward E. Cancer statistics, 2010. CA Cancer J. Clin. 2010, 60:277-300.
4. Philip P.A., Mooney M., Jaffe D., Eckhardt G., Moore M., Meropol N., Emens L., O'Reilly E., Korc M., Ellis L., Benedetti J., Rothenberg M., Willett C., Tempero M., Lowy A., Abbruzzese J., Simeone D., Hingorani S., Berlin J., Tepper J. Consensus report of the National Cancer Institute clinical trials planning meeting on pancreas cancer treatment. J. Clin. Oncol. 2009, 27:5660-5669.
5. Rosenberg L. Treatment of pancreatic cancer. Promises and problems of tamoxifen, somatostatin analogs, and gemcitabine. Int. J. Pancreatol. 1997, 22:81-93.
6. Rothenberg M.L., Moore M.J., Cripps M.C., Andersen J.S., Portenoy R.K., Burris H.A., Green M.R., Tarassoff P.G., Brown T.D., Casper E.S., Storniolo A.M., Von Hoff D.D. A phase II trial of gemcitabine in patients with 5-FU-refractory pancreas cancer. Ann. Oncol. 1996, 7:347-353.
7. Warshaw A.L., Fernandez-del Castillo C. Pancreatic carcinoma. N. Engl. J. Med. 1992, 326:455-465.
8. Conroy T., Desseigne F., Ychou M., Bouche O., Guimbaud R., Becouarn Y., Adenis A., Raoul J.L., Gourgou-Bourgade S., de la Fouchardiere C., Bennouna J., Bachet J.B., Khemissa-Akouz F., Pere-Verge D., Delbaldo C., Assenat E., Chauffert B., Michel P., Montoto-Grillot C., Ducreux M. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N. Engl. J. Med. 2011, 364:1817-1825.
9. Moore M.J., Goldstein D., Hamm J., Figer A., Hecht J.R., Gallinger S., Au H.J., Murawa P., Walde D., Wolff R.A., Campos D., Lim R., Ding K., Clark G., Voskoglou-Nomikos T., Ptasynski M., Parulekar W. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J. Clin. Oncol. 2007, 25:1960-1966.
10. Collisson E.A., Sadanandam A., Olson P., Gibb W.J., Truitt M., Gu S., Cooc J., Weinkle J., Kim G.E., Jakkula L., Feiler H.S., Ko A.H., Olshen A.B., Danenberg K.L., Tempero M.A., Spellman P.T., Hanahan D., Gray J.W. Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy. Nat. Med. 2011, 17:500-503.
11. Hebrok M., Kim S.K., Melton D.A. Notochord repression of endodermal Sonic hedgehog permits pancreas development. Genes Dev. 1998, 12:1705-1713.
12. Sellick G.S., Barker K.T., Stolte-Dijkstra I., Fleischmann C., Coleman R.J., Garrett C., Gloyn A.L., Edghill E.L., Hattersley A.T., Wellauer P.K., Goodwin G., Houlston R.S. Mutations in PTF1A cause pancreatic and cerebellar agenesis. Nat. Genet. 2004, 36:1301-1305.
13. Fukuda A., Kawaguchi Y., Furuyama K., Kodama S., Horiguchi M., Kuhara T., Koizumi M., Boyer D.F., Fujimoto K., Doi R., Kageyama R., Wright C.V., Chiba T. Ectopic pancreas formation in Hes1-knockout mice reveals plasticity of endodermal progenitors of the gut, bile duct, and pancreas. J. Clin. Invest. 2006, 116:1484-1493.
14. Lin J.W., Biankin A.V., Horb M.E., Ghosh B., Prasad N.B., Yee N.S., Pack M.A., Leach S.D. Differential requirement for ptf1a in endocrine and exocrine lineages of developing zebrafish pancreas. Dev. Biol. 2004, 274:491-503.
15. Duvillie B., Attali M., Bounacer A., Ravassard P., Basmaciogullari A., Scharfmann R. The mesenchyme controls the timing of pancreatic beta-cell differentiation. Diabetes 2006, 55:582-589.
16. Gu G., Dubauskaite J., Melton D.A. Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors. Development 2002, 129:2447-2457.
17. Schwitzgebel V.M., Scheel D.W., Conners J.R., Kalamaras J., Lee J.E., Anderson D.J., Sussel L., Johnson J.D., German M.S. Expression of neurogenin3 reveals an islet cell precursor population in the pancreas. Development 2000, 127:3533-3542.
18. Zhou Q., Brown J., Kanarek A., Rajagopal J., Melton D.A. In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature 2008, 455:627-632.
19. Collombat P., Mansouri A., Hecksher-Sorensen J., Serup P., Krull J., Gradwohl G., Gruss P. Opposing actions of Arx and Pax4 in endocrine pancreas development. Genes Dev. 2003, 17:2591-2603.
20. Sosa-Pineda B. The gene Pax4 is an essential regulator of pancreatic beta-cell development. Mol. Cells 2004, 18:289-294.
21. Dor Y., Melton D.A. How important are adult stem cells for tissue maintenance?. Cell Cycle 2004, 3:1104-1106.
22. Fujikura J., Hosoda K., Iwakura H., Tomita T., Noguchi M., Masuzaki H., Tanigaki K., Yabe D., Honjo T., Nakao K. Notch/Rbp-j signaling prevents premature endocrine and ductal cell differentiation in the pancreas. Cell Metab. 2006, 3:59-65.
23. Murtaugh L.C., Stanger B.Z., Kwan K.M., Melton D.A. Notch signaling controls multiple steps of pancreatic differentiation. Proc. Natl. Acad. Sci. U.S.A. 2003, 100:14920-14925.
24. Zhu L., Gibson P., Currle D.S., Tong Y., Richardson R.J., Bayazitov I.T., Poppleton H., Zakharenko S., Ellison D.W., Gilbertson R.J. Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation. Nature 2009, 457:603-607.
25. Oshima Y., Suzuki A., Kawashimo K., Ishikawa M., Ohkohchi N., Taniguchi H. Isolation of mouse pancreatic ductal progenitor cells expressing CD133 and c-Met by flow cytometric cell sorting. Gastroenterology 2007, 132:720-732.
26. Hingorani S., Wang L., Multani A., Combs C., Deramaudt T., Hruban R., Rustgi A., Chang S., Tuveson D. Trp53 and Kras cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell 2005, 7:469-483.
27. Bardeesy N., Aguirre A.J., Chu G.C., Cheng K.H., Lopez L.V., Hezel A.F., Feng B., Brennan C., Weissleder R., Mahmood U., Hanahan D., Redston M.S., Chin L., Depinho R.A. Both p16(Ink4a) and the p19(Arf)-p53 pathway constrain progression of pancreatic adenocarcinoma in the mouse. Proc. Natl. Acad. Sci. U.S.A. 2006, 103:5947-5952.
28. Morton J.P., Timpson P., Karim S.A., Ridgway R.A., Athineos D., Doyle B., Jamieson N.B., Oien K.A., Lowy A.M., Brunton V.G., Frame M.C., Evans T.R., Sansom O.J. Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer. Proc. Natl. Acad. Sci. U.S.A. 2011, 107:246-251.
29. Brembeck F.H., Schreiber F.S., Deramaudt T.B., Craig L., Rhoades B., Swain G., Grippo P., Stoffers D.A., Silberg D.G., Rustgi A.K. The mutant K-ras oncogene causes pancreatic periductal lymphocytic infiltration and gastric mucous neck cell hyperplasia in transgenic mice. Cancer Res. 2003, 63:2005-2009.
30. Gidekel Friedlander S.Y., Chu G.C., Snyder E.L., Girnius N., Dibelius G., Crowley D., Vasile E., DePinho R.A., Jacks T. Context-dependent transformation of adult pancreatic cells by oncogenic K-Ras. Cancer Cell 2009, 16:379-389.
31. Prasad N.B., Biankin A.V., Fukushima N., Maitra A., Dhara S., Elkahloun A.G., Hruban R.H., Goggins M., Leach S.D. Gene expression profiles in pancreatic intraepithelial neoplasia reflect the effects of Hedgehog signaling on pancreatic ductal epithelial cells. Cancer Res. 2005, 65:1619-1626.
32. Strobel O., Dor Y., Alsina J., Stirman A., Lauwers G., Trainor A., Castillo C.F., Warshaw A.L., Thayer S.P. In vivo lineage tracing defines the role of acinar-to-ductal transdifferentiation in inflammatory ductal metaplasia. Gastroenterology 2007, 133:1999-2009.
33. Grippo P.J., Nowlin P.S., Demeure M.J., Longnecker D.S., Sandgren E.P. Preinvasive pancreatic neoplasia of ductal phenotype induced by acinar cell targeting of mutant Kras in transgenic mice. Cancer Res. 2003, 63:2016-2019.
34. De La O.J., Murtaugh L.C. Notch and Kras in pancreatic cancer: at the crossroads of mutation, differentiation and signaling. Cell Cycle 2009, 8:1860-1864.
35. Sangiorgi E., Capecchi M.R. Bmi1 lineage tracing identifies a self-renewing pancreatic acinar cell subpopulation capable of maintaining pancreatic organ homeostasis. Proc. Natl. Acad. Sci. U.S.A. 2009, 106:7101-7106.
36. Stanger B.Z., Dor Y. Dissecting the cellular origins of pancreatic cancer. Cell Cycle 2006, 5:43-46.
37. Stanger B.Z., Stiles B., Lauwers G.Y., Bardeesy N., Mendoza M., Wang Y., Greenwood A., Cheng K.H., McLaughlin M., Brown D., Depinho R.A., Wu H., Melton D.A., Dor Y. Pten constrains centroacinar cell expansion and malignant transformation in the pancreas. Cancer Cell 2005, 8:185-195.
38. Hebrok M., Kim S.K., St Jacques B., McMahon A.P., Melton D.A. Regulation of pancreas development by hedgehog signaling. Development 2000, 127:4905-4913.
39. Malka D., Hammel P., Maire F., Rufat P., Madeira I., Pessione F., Levy P., Ruszniewski P. Risk of pancreatic adenocarcinoma in chronic pancreatitis. Gut 2002, 51:849-852.
40. Rebours V., Levy P., Mosnier J.F., Scoazec J.Y., Soubeyrand M.S., Flejou J.F., Turlin B., Hammel P., Ruszniewski P., Bedossa P., Couvelard A. Pathology analysis reveals that dysplastic pancreatic ductal lesions are frequent in patients with hereditary pancreatitis. Clin. Gastroenterol. Hepatol. 2010, 8:206-212.
41. Raimondi S., Maisonneuve P., Lowenfels A.B. Epidemiology of pancreatic cancer: an overview. Nat. Rev. Gastroenterol. Hepatol. 2009, 6:699-708.
42. Guerra C., Schuhmacher A.J., Canamero M., Grippo P.J., Verdaguer L., Perez-Gallego L., Dubus P., Sandgren E.P., Barbacid M. Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice. Cancer Cell 2007, 11:291-302.
43. Greten F.R., Eckmann L., Greten T.F., Park J.M., Li Z.W., Egan L.J., Kagnoff M.F., Karin M. IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 2004, 118:285-296.
44. Xu X., Dhoker J., Stange G., Bonne S., Deleu N., Xiao X., Vandecasteele M., Mellitzer G., Ling Z., Pipeleers D. β Cells can be generated from endogenous progenitors in injured adult mouse pancreas. Cell 2008, 132:197-207.
45. Li C., Heidt D.G., Dalerba P., Burant C.F., Zhang L., Adsay V., Wicha M., Clarke M.F., Simeone D.M. Identification of pancreatic cancer stem cells. Cancer Res. 2007, 67:1030-1037.
46. Hermann P.C., Huber S.L., Herrler T., Aicher A., Ellwart J.W., Guba M., Bruns C.J., Heeschen C. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 2007, 1:313-323.
47. Li C., Wu J.J., Hynes M., Dosch J., Sarkar B., Welling T.H., di Magliano M.P., Simeone D.M. c-Met is a marker of pancreatic cancer stem cells and therapeutic target. Gastroenterology 2011, 141(6):2218-2227.e5. (Electronic publication ahead of print 2011 Aug 22).
48. Rasheed Z.A., Yang J., Wang Q., Kowalski J., Freed I., Murter C., Hong S.M., Koorstra J.B., Rajeshkumar N.V., He X., Goggins M., Iacobuzio-Donahue C., Berman D.M., Laheru D., Jimeno A., Hidalgo M., Maitra A., Matsui W. Prognostic significance of tumorigenic cells with mesenchymal features in pancreatic adenocarcinoma. J. Natl. Cancer Inst. 2010, 102:340-351.
49. Bankert R.B., Balu-Iyer S.V., Odunsi K., Shultz L.D., Kelleher R.J., Barnas J.L., Simpson-Abelson M., Parsons R., Yokota S.J. Humanized mouse model of ovarian cancer recapitulates patient solid tumor progression, ascites formation, and metastasis. PLoS One 2011, 6:e24420.
50. Schmitz M., Breithaupt P., Scheidegger N., Cario G., Bonapace L., Meissner B., Mirkowska P., Tchinda J., Niggli F.K., Stanulla M., Schrappe M., Schrauder A., Bornhauser B.C., Bourquin J.P. Xenografts of highly resistant leukemia recapitulate the clonal composition of the leukemogenic compartment. Blood 2011, 118:1854-1864.
51. Lonardo E., Hermann P.C., Mueller M.-T., Huber S., Balic A., Miranda-Lorenzo I., Zagorac S., Alcala S., Rodriguez-Arabaolaza I., Ramirez J.C., Torres-Ruíz R., Garcia E., Hidaldo M., Cebrián D.Á., Heuchel R., Löhr M., Berger F., Bartenstein P., Aicher A., Heeschen C. Nodal/Activin signaling drives self-renewal and tumorigenicity of pancreatic cancer stem cells and provides a target for combined drug therapy. Cell Stem Cell 2011, 9(5):433-446.
52. Mueller M.T., Hermann P.C., Witthauer J., Rubio-Viqueira B., Leicht S.F., Huber S., Ellwart J.W., Mustafa M., Bartenstein P., D'Haese J.G., Schoenberg M.H., Berger F., Jauch K.W., Hidalgo M., Heeschen C. Combined targeted treatment to eliminate tumorigenic cancer stem cells in human pancreatic cancer. Gastroenterology 2009, 137:1102-1113.
53. Rubio-Viqueira B., Jimeno A., Cusatis G., Zhang X., Iacobuzio-Donahue C., Karikari C., Shi C., Danenberg K., Danenberg P.V., Kuramochi H., Tanaka K., Singh S., Salimi-Moosavi H., Bouraoud N., Amador M.L., Altiok S., Kulesza P., Yeo C., Messersmith W., Eshleman J., Hruban R.H., Maitra A., Hidalgo M. An in vivo platform for translational drug development in pancreatic cancer. Clin. Cancer Res. 2006, 12:4652-4661.
54. Lathia J.D., Gallagher J., Myers J.T., Li M., Vasanji A., McLendon R.E., Hjelmeland A.B., Huang A.Y., Rich J.N. Direct in vivo evidence for tumor propagation by glioblastoma cancer stem cells. PLoS One 2011, 6:e24807.
55. Al-Hajj M., Wicha M.S., Benito-Hernandez A., Morrison S., Clarke M.F. Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. U.S.A. 2003, 100:3983-3988.
56. Gao M.Q., Choi Y.P., Kang S., Youn J.H., Cho N.H. CD24(+) cells from hierarchically organized ovarian cancer are enriched in cancer stem cells. Oncogene 2010, 29:2672-2680.
57. Feldmann G., Dhara S., Fendrich V., Bedja D., Beaty R., Mullendore M., Karikari C., Alvarez H., Iacobuzio-Donahue C., Jimeno A., Gabrielson K.L., Matsui W., Maitra A. Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: a new paradigm for combination therapy in solid cancers. Cancer Res. 2007, 67:2187-2196.
58. Jimeno A., Feldmann G., Suarez-Gauthier A., Rasheed Z., Solomon A., Zou G.M., Rubio-Viqueira B., Garcia-Garcia E., Lopez-Rios F., Matsui W., Maitra A., Hidalgo M. A direct pancreatic cancer xenograft model as a platform for cancer stem cell therapeutic development. Mol. Cancer Ther. 2009, 8:310-314.
59. Deng S., Yang X., Lassus H., Liang S., Kaur S., Ye Q., Li C., Wang L.P., Roby K.F., Orsulic S., Connolly D.C., Zhang Y., Montone K., Butzow R., Coukos G., Zhang L. Distinct expression levels and patterns of stem cell marker, aldehyde dehydrogenase isoform 1 (ALDH1), in human epithelial cancers. PLoS One 2010, 5:e10277.
60. Campbell P.J., Yachida S., Mudie L.J., Stephens P.J., Pleasance E.D., Stebbings L.A., Morsberger L.A., Latimer C., McLaren S., Lin M.L., McBride D.J., Varela I., Nik-Zainal S.A., Leroy C., Jia M., Menzies A., Butler A.P., Teague J.W., Griffin C.A., Burton J., Swerdlow H., Quail M.A., Stratton M.R., Iacobuzio-Donahue C., Futreal P.A. The patterns and dynamics of genomic instability in metastatic pancreatic cancer. Nature 2010, 467:1109-1113.
61. Yachida S., Jones S., Bozic I., Antal T., Leary R., Fu B., Kamiyama M., Hruban R.H., Eshleman J.R., Nowak M.A., Velculescu V.E., Kinzler K.W., Vogelstein B., Iacobuzio-Donahue C.A. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 2010, 467:1114-1117.
62. Notta F., Mullighan C.G., Wang J.C., Poeppl A., Doulatov S., Phillips L.A., Ma J., Minden M.D., Downing J.R., Dick J.E. Evolution of human BCR-ABL1 lymphoblastic leukaemia-initiating cells. Nature 2011, 469:362-367.
63. Jones R.J., Matsui W.H., Smith B.D. Cancer stem cells: are we missing the target?. J. Natl. Cancer Inst. 2004, 96:583-585.
64. Kayali A.G., Van Gunst K., Campbell I.L., Stotland A., Kritzik M., Liu G., Flodstrom-Tullberg M., Zhang Y.Q., Sarvetnick N. The stromal cell-derived factor-1alpha/CXCR4 ligand-receptor axis is critical for progenitor survival and migration in the pancreas. J. Cell Biol. 2003, 163:859-869.
65. Kucia M., Reca R., Miekus K., Wanzeck J., Wojakowski W., Janowska-Wieczorek A., Ratajczak J., Ratajczak M.Z. Trafficking of normal stem cells and metastasis of cancer stem cells involve similar mechanisms: pivotal role of the SDF-1-CXCR4 axis. Stem Cells 2005, 23:879-894.
66. Murakami T., Maki W., Cardones A.R., Fang H., Tun Kyi A., Nestle F.O., Hwang S.T. Expression of CXC chemokine receptor-4 enhances the pulmonary metastatic potential of murine B16 melanoma cells. Cancer Res. 2002, 62:7328-7334.
67. Nakata B., Fukunaga S., Noda E., Amano R., Yamada N., Hirakawa K. Chemokine receptor CCR7 expression correlates with lymph node metastasis in pancreatic cancer. Oncology 2008, 74:69-75.
68. Wellner U., Schubert J., Burk U.C., Schmalhofer O., Zhu F., Sonntag A., Waldvogel B., Vannier C., Darling D., zur Hausen A., Brunton V.G., Morton J., Sansom O., Schuler J., Stemmler M.P., Herzberger C., Hopt U., Keck T., Brabletz S., Brabletz T. The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nat. Cell Biol. 2009, 11:1487-1495.
69. Gupta P.B., Chaffer C.L., Weinberg R.A. Cancer stem cells: mirage or reality?. Nat. Med. 2009, 15:1010-1012.
70. Iliopoulos D., Hirsch H.A., Wang G., Struhl K. Inducible formation of breast cancer stem cells and their dynamic equilibrium with non-stem cancer cells via IL6 secretion. Proc. Natl. Acad. Sci. U.S.A. 2011, 108:1397-1402.
71. Alunni-Fabbroni M., Sandri M.T. Circulating tumour cells in clinical practice: methods of detection and possible characterization. Methods 2010, 50:289-297.
72. Pantel K., Brakenhoff R.H., Brandt B. Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat. Rev. Cancer 2008, 8:329-340.
73. Tan S.J., Lakshmi R.L., Chen P., Lim W.T., Yobas L., Lim C.T. Versatile label free biochip for the detection of circulating tumor cells from peripheral blood in cancer patients. Biosens. Bioelectron. 2010, 26:1701-1705.
74. Goodell M.A., Brose K., Paradis G., Conner A.S., Mulligan R.C. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J. Exp. Med. 1996, 183:1797-1806.
75. Visvader J.E., Lindeman G.J. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat. Rev. Cancer 2008, 8:755-768.
76. Lonardo E., Hermann P.C., Heeschen C. Pancreatic cancer stem cells - update and future perspectives. Mol. Oncol. 2010, 4:431-442.
77. Ingham P.W., McMahon A.P. Hedgehog signaling in animal development: paradigms and principles. Genes Dev. 2001, 15:3059-3087.
78. Berman D., Karhadkar S., Maitra A., Montes De Oca R., Gerstenblith M., Briggs K., Parker A., Shimada Y., Eshleman J., Watkins D., Beachy P. Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nature 2003, 425:846-851.
79. Gould K.L., Martucci J.P., Goldberg D.I., Hess M.J., Edens R.P., Latifi R., Dudrick S.J. Short-term cholesterol lowering decreases size and severity of perfusion abnormalities by positron emission tomography after dipyridamole in patients with coronary artery disease. A potential noninvasive marker of healing coronary endothelium. Circulation 1994, 89:1530-1538.
80. Gould A., Missailidis S. Targeting the hedgehog pathway: the development of cyclopamine and the development of anti-cancer drugs targeting the hedgehog pathway. Mini Rev. Med. Chem. 2011, 11:200-213.
81. Dosch J.S., Pasca di Magliano M., Simeone D.M. Pancreatic cancer and hedgehog pathway signaling: new insights. Pancreatology 2010, 10:151-157.
82. Mihaljevic A.L., Michalski C.W., Friess H., Kleeff J. Molecular mechanism of pancreatic cancer-understanding proliferation, invasion, and metastasis. Langenbecks Arch. Surg. 2010, 395:295-308.
83. Lauth M., Rohnalter V., Bergstrom A., Kooshesh M., Svenningsson P., Toftgard R. Antipsychotic drugs regulate hedgehog signaling by modulation of 7-dehydrocholesterol reductase levels. Mol. Pharmacol. 2010, 78:486-496.
84. Dimou A., Syrigos K., Saif M.W. Rationale for inhibition of the hedgehog pathway paracrine loop in pancreatic adenocarcinoma. JOP 2011, 12:1-5.
85. Perugini R.A., McDade T.P., Vittimberga F.J., Callery M.P. Pancreatic cancer cell proliferation is phosphatidylinositol 3-kinase dependent. J. Surg. Res. 2000, 90:39-44.
86. Ng S.S.W., Tsao M.S., Chow S., Hedley D.W. Inhibition of phosphatidylinositide 3-kinase enhances gemcitabine-induced apoptosis in human pancreatic cancer cells. Cancer Res. 2000, 60:5451-5455.
87. Wang Z., Zhang Y., Banerjee S., Li Y., Sarkar F.H. Notch-1 down-regulation by curcumin is associated with the inhibition of cell growth and the induction of apoptosis in pancreatic cancer cells. Cancer 2006, 106:2503-2513.
88. Bao S., Wu Q., Mclendon R., Hao Y., Shi Q., Hjelmeland A., Dewhirst M., Bigner D., Rich J. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 2006, 444:756-760.
89. Mukhopadhyay A., Bueso-Ramos C., Chatterjee D., Pantazis P., Aggarwal B.B. Curcumin downregulates cell survival mechanisms in human prostate cancer cell lines. Oncogene 2001, 20:7597-7609.
90. Sarkar F.H., Li Y. Cell signaling pathways altered by natural chemopreventive agents. Mutat. Res. 2004, 555:53-64.
91. Shay J.W., Wright W.E. Telomeres and telomerase in normal and cancer stem cells. FEBS Lett. 2010, 584:3819-3825.
92. Flores I., Canela A., Vera E., Tejera A., Cotsarelis G., Blasco M.A. The longest telomeres: a general signature of adult stem cell compartments. Genes Dev. 2008, 22:654-667.
93. Phatak P., Burger A.M. Telomerase and its potential for therapeutic intervention. Br. J. Pharmacol. 2007, 152:1003-1011.
94. Joseph A.M., Norman S.M., Ferry L.H., Prochazka A.V., Westman E.C., Steele B.G., Sherman S.E., Cleveland M., Antonnucio D.O., Hartman N., McGovern P.G. The safety of transdermal nicotine as an aid to smoking cessation in patients with cardiac disease. N. Engl. J. Med. 1996, 335:1792-1798.
95. Busillo J.M., Benovic J.L. Regulation of CXCR4 signaling. Biochim. Biophys. Acta 2007, 1768:952-963.
96. Furusato B., Mohamed A., Uhlen M., Rhim J.S. CXCR4 and cancer. Pathol. Int. 2010, 60:497-505.
97. Mori T., Doi R., Koizumi M., Toyoda E., Ito D., Kami K., Masui T., Fujimoto K., Tamamura H., Hiramatsu K., Fujii N., Imamura M. CXCR4 antagonist inhibits stromal cell-derived factor 1-induced migration and invasion of human pancreatic cancer. Mol. Cancer Ther. 2004, 3:29-37.
98. Saur D., Seidler B., Schneider G., Algul H., Beck R., Senekowitsch-Schmidtke R., Schwaiger M., Schmid R.M. CXCR4 expression increases liver and lung metastasis in a mouse model of pancreatic cancer. Gastroenterology 2005, 129:1237-1250.
99. Matsuo Y., Ochi N., Sawai H., Yasuda A., Takahashi H., Funahashi H., Takeyama H., Tong Z., Guha S. CXCL8/IL-8 and CXCL12/SDF-1alpha co-operatively promote invasiveness and angiogenesis in pancreatic cancer. Int. J. Cancer 2009, 124:853-861.
100. Singh S., Srivastava S.K., Bhardwaj A., Owen L.B., Singh A.P. CXCL12-CXCR4 signalling axis confers gemcitabine resistance to pancreatic cancer cells: a novel target for therapy. Br. J. Cancer 2010, 103:1671-1679.
101. Hendrix C.W., Collier A.C., Lederman M.M., Schols D., Pollard R.B., Brown S., Jackson J.B., Coombs R.W., Glesby M.J., Flexner C.W., Bridger G.J., Badel K., MacFarland R.T., Henson G.W., Calandra G. Safety, pharmacokinetics, and antiviral activity of AMD3100, a selective CXCR4 receptor inhibitor, in HIV-1 infection. J. Acquir. Immune Defic. Syndr. 2004, 37:1253-1262.
102. Kalatskaya I., Berchiche Y.A., Gravel S., Limberg B.J., Rosenbaum J.S., Heveker N. AMD3100 is a CXCR7 ligand with allosteric agonist properties. Mol. Pharmacol. 2009, 75:1240-1247.
103. Burger J.A., Stewart D.J. CXCR4 chemokine receptor antagonists: perspectives in SCLC. Expert Opin. Investig. Drugs 2009, 18:481-490.
104. Park B., Sung B., Yadav V.R., Cho S.G., Liu M., Aggarwal B.B. Acetyl-11-keto-beta-boswellic acid suppresses invasion of pancreatic cancer cells through the downregulation of CXCR4 chemokine receptor expression. Int. J. Cancer 2011, 129:23-33.
105. Yadav V.R., Sung B., Prasad S., Kannappan R., Cho S.G., Liu M., Chaturvedi M.M., Aggarwal B.B. Celastrol suppresses invasion of colon and pancreatic cancer cells through the downregulation of expression of CXCR4 chemokine receptor. J. Mol. Med. 2010, 88:1243-1253.
106. Fearon E.R., Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 1990, 61:759-767.
107. Jones S., Zhang X., Parsons D.W., Lin J.C., Leary R.J., Angenendt P., Mankoo P., Carter H., Kamiyama H., Jimeno A., Hong S.M., Fu B., Lin M.T., Calhoun E.S., Kamiyama M., Walter K., Nikolskaya T., Nikolsky Y., Hartigan J., Smith D.R., Hidalgo M., Leach S.D., Klein A.P., Jaffee E.M., Goggins M., Maitra A., Iacobuzio-Donahue C., Eshleman J.R., Kern S.E., Hruban R.H., Karchin R., Papadopoulos N., Parmigiani G., Vogelstein B., Velculescu V.E., Kinzler K.W. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 2008, 321:1801-1806.
108. Hermann P.C., Bhaskar S., Cioffi M., Heeschen C. Cancer stem cells in solid tumors. Semin. Cancer Biol. 2010, 20:77-84.