Loss of STAT3 in lymphoma relaxes NK cell-mediated tumor surveillance

Cancers

Volumn 6, Issue 1, 2014, Pages 193-210

  Putz, Eva Maria ^a   Hoelzl, Maria Agnes ^b   Baeck, Julia ^a   Bago Horvath, Zsuzsanna ^a,b   Schuster, Christian ^b   Reichholf, Brian ^a   Kern, Daniela ^c   Aberger, Fritz ^c   Sexl, Veronika ^a   Hoelbl Kovacic, Andrea ^a  

^a UNIVERSITY OF VETERINARY MEDICINE   (Austria)

^b MEDICAL UNIVERSITY OF VIENNA   (Austria)

^c UNIVERSITY OF SALZBURG   (Austria)

Author keywords

Bcr abl; Lymphoma; Nk cells; Stat3; Tumor immune surveillance

Indexed keywords

BCR ABL PROTEIN; GAMMA INTERFERON; INTERLEUKIN 6; RANTES; STAT3 PROTEIN; TUMOR NECROSIS FACTOR ALPHA;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; B LYMPHOCYTE; CELL MEDIATED CYTOTOXICITY; CELL PROLIFERATION; CONTROLLED STUDY; IMMUNOSURVEILLANCE; KNOCKOUT MOUSE; LYMPHOMA; MOUSE MODEL; NATURAL KILLER CELL; NONHUMAN; TUMOR ASSOCIATED LEUKOCYTE; TUMOR GROWTH; TUMOR VOLUME;

EID: 84893429068     PISSN: None     EISSN: 20726694     Source Type: Journal    
DOI: 10.3390/cancers6010193     Document Type: Article

References (65)

1. Hanahan, D.; Weinberg, R.A. The hallmarks of cancer. Cell 2000, 100, 57-70.
2. Weinstein, I.B. Cancer. Addiction to oncogenes-The Achilles heal of cancer. Science 2002, 297, 63-64.
3. Luo, J.; Solimini, N.L.; Elledge, S.J. Principles of cancer therapy: Oncogene and non-oncogene addiction. Cell 2009, 136, 823-837.
4. Bowman, T.; Garcia, R.; Turkson, J.; Jove, R. STATs in oncogenesis. Oncogene 2000, 19, 2474-2488.
5. Yu, H.; Jove, R. The STATs of cancer-New molecular targets come of age. Nat. Rev. Cancer 2004, 4, 97-105.
6. Ling, X.; Arlinghaus, R.B. Knockdown of STAT3 expression by RNA interference inhibits the induction of breast tumors in immunocompetent mice. Cancer Res. 2005, 65, 2532-2536.
7. Bar-Natan, M.; Nelson, E.A.; Xiang, M.; Frank, D.A. STAT signaling in the pathogenesis and treatment of myeloid malignancies. JAK-STAT 2012, 1, 55-64.
8. Hoelbl, A.; Schuster, C.; Kovacic, B.; Zhu, B.; Wickre, M.; Hoelzl, M.A.; Fajmann, S.; Grebien, F.; Warsch, W.; Stengl, G., et al. Stat5 is indispensable for the maintenance of bcr/abl-positive leukaemia. EMBO Mol. Med. 2010, 2, 98-110.
9. Bromberg, J. Stat proteins and oncogenesis. J. Clin. Investig. 2002, 109, 1139-1142.
10. Buettner, R.; Mora, L.B.; Jove, R. Activated STAT signaling in human tumors provides novel molecular targets for therapeutic intervention. Clin. Cancer Res. 2002, 8, 945-954.
11. Azare, J.; Leslie, K.; Al-Ahmadie, H.; Gerald, W.; Weinreb, P.H.; Violette, S.M.; Bromberg, J. Constitutively activated Stat3 induces tumorigenesis and enhances cell motility of prostate epithelial cells through integrin beta 6. Mol. Cell Biol. 2007, 27, 4444-4453.
12. Abdulghani, J.; Gu, L.; Dagvadorj, A.; Lutz, J.; Leiby, B.; Bonuccelli, G.; Lisanti, M.P.; Zellweger, T.; Alanen, K.; Mirtti, T., et al. Stat3 promotes metastatic progression of prostate cancer. Am. J. Pathol. 2008, 172, 1717-1728.
13. Barbieri, I.; Pensa, S.; Pannellini, T.; Quaglino, E.; Maritano, D.; Demaria, M.; Voster, A.; Turkson, J.; Cavallo, F.; Watson, C.J., et al. Constitutively active Stat3 enhances neu-mediated migration and metastasis in mammary tumors via upregulation of Cten. Cancer Res. 2010, 70, 2558-2567.
14. Gough, D.J.; Corlett, A.; Schlessinger, K.; Wegrzyn, J.; Larner, A.C.; Levy, D.E. Mitochondrial STAT3 supports Ras-dependent oncogenic transformation. Science 2009, 324, 1713-1716.
15. Zhang, Q.; Raje, V.; Yakovlev, V.A.; Yacoub, A.; Szczepanek, K.; Meier, J.; Derecka, M.; Chen, Q.; Hu, Y.; Sisler, J., et al. Mitochondrial localized Stat3 promotes breast cancer growth via phosphorylation of serine 727. J. Biol. Chem. 2013, 288, 31280-31288.
16. Kim, D.J.; Angel, J.M.; Sano, S.; DiGiovanni, J. Constitutive activation and targeted disruption of signal transducer and activator of transcription 3 (Stat3) in mouse epidermis reveal its critical role in UVB-induced skin carcinogenesis. Oncogene 2009, 28, 950-960.
17. Weber-Nordt, R.M.; Egen, C.; Wehinger, J.; Ludwig, W.; Gouilleux-Gruart, V.; Mertelsmann, R.; Finke, J. Constitutive activation of STAT proteins in primary lymphoid and myeloid leukemia cells and in Epstein-Barr virus (EBV)-related lymphoma cell lines. Blood 1996, 88, 809-816.
18. Lin, T.S.; Mahajan, S.; Frank, D.A. STAT signaling in the pathogenesis and treatment of leukemias. Oncogene 2000, 19, 2496-2504.
19. Benekli, M.; Baer, M.R.; Baumann, H.; Wetzler, M. Signal transducer and activator of transcription proteins in leukemias. Blood 2003, 101, 2940-2954.
20. Benekli, M.; Baumann, H.; Wetzler, M. Targeting signal transducer and activator of transcription signaling pathway in leukemias. J. Clin. Oncol. 2009, 27, 4422-4432.
21. Ecker, A.; Simma, O.; Hoelbl, A.; Kenner, L.; Beug, H.; Moriggl, R.; Sexl, V. The dark and the bright side of Stat3: Proto-oncogene and tumor-suppressor. Front. Biosci. 2009, 14, 2944-2958.
22. Lee, J.; Kim, J.C.K.; Lee, S.-E.; Quinley, C.; Kim, H.; Herdman, S.; Corr, M.; Raz, E. Signal transducer and activator of transcription 3 (STAT3) protein suppresses adenoma-to-carcinoma transition in Apcmin/+ mice via regulation of Snail-1 (SNAI) protein stability. J. Biol. Chem. 2012, 287, 18182-18189.
23. De la Iglesia, N.; Konopka, G.; Puram, S.V.; Chan, J.A.; Bachoo, R.M.; You, M.J.; Levy, D.E.; Depinho, R.A.; Bonni, A. Identification of a PTEN-regulated STAT3 brain tumor suppressor pathway. Genes Dev. 2008, 22, 449-462.
24. Musteanu, M.; Blaas, L.; Mair, M.; Schlederer, M.; Bilban, M.; Tauber, S.; Esterbauer, H.; Mueller, M.; Casanova, E.; Kenner, L., et al. Stat3 is a negative regulator of intestinal tumor progression in Apc(Min) mice. Gastroenterology 2010, 138, 1003-1011.e5.
25. Mair, M.; Zollner, G.; Schneller, D.; Musteanu, M.; Fickert, P.; Gumhold, J.; Schuster, C.; Fuchsbichler, A.; Bilban, M.; Tauber, S., et al. Signal transducer and activator of transcription 3 protects from liver injury and fibrosis in a mouse model of sclerosing cholangitis. Gastroenterology 2010, 138, 2499-2508.
26. Vesely, M.D.; Kershaw, M.H.; Schreiber, R.D.; Smyth, M.J. Natural innate and adaptive immunity to cancer. Annu. Rev. Immunol. 2011, 29, 235-271.
27. Stoiber, D.; Kovacic, B.; Schuster, C.; Schellack, C.; Karaghiosoff, M.; Kreibich, R.; Weisz, E.; Artwohl, M.; Kleine, O.C.; Müller, M., et al. TYK2 is a key regulator of the surveillance of B lymphoid tumors. J. Clin. Investig. 2004, 114, 1650-1658.
28. Kovacic, B.; Stoiber, D.; Moriggl, R.; Weisz, E.; Ott, R.G.; Kreibich, R.; Levy, D.E.; Beug, H.; Freissmuth, M.; Sexl, V. STAT1 acts as a tumor promoter for leukemia development. Cancer Cell 2006, 10, 77-87.
29. Baron, F.; Turhan, A.G.; Giron-Michel, J.; Azzarone, B.; Bentires-Alj, M.; Bours, V.; Bourhis, J.H.; Chouaib, S.; Caignard, A. Leukemic target susceptibility to natural killer cytotoxicity: Relationship with BCR-ABL expression. Blood 2002, 99, 2107-2113.
30. Maghazachi, A.A. Role of chemokines in the biology of natural killer cells. Curr. Top. Microbiol. Immunol. 2010, 341, 37-58.
31. Kärre, K.; Ljunggren, H.G.; Piontek, G.; Kiessling, R.; Karre, K. Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature 1986, 319, 675-678.
32. Raulet, D.H.; Guerra, N. Oncogenic stress sensed by the immune system: Role of natural killer cell receptors. Nat. Rev. Immunol. 2009, 9, 568-580.
33. Yu, H.; Pardoll, D.; Jove, R. STATs in cancer inflammation and immunity: A leading role for STAT3. Nat. Rev. Cancer 2009, 9, 798-809.
34. Lee, H.; Pal, S.K.; Reckamp, K.; Figlin, R.A.; Yu, H. STAT3: A target to enhance antitumor immune response. Curr. Top. Microbiol. Immunol. 2011, 344, 41-59.
35. Niu, G.; Wright, K.L.; Huang, M.; Song, L.; Haura, E.; Turkson, J.; Zhang, S.; Wang, T.; Sinibaldi, D.; Coppola, D., et al. Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis. Oncogene 2002, 21, 2000-2008.
36. Kortylewski, M.; Yu, H. Role of Stat3 in suppressing anti-tumor immunity. Curr. Opin. Immunol. 2008, 20, 228-233.
37. Kortylewski, M.; Kujawski, M.; Wang, T.; Wei, S.; Zhang, S.; Pilon-Thomas, S.; Niu, G.; Kay, H.; Mule, J.; Kerr, W.G., et al. Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity. Nat. Med. 2005, 11, 1314-1321.
38. Alonzi, T.; Maritano, D.; Gorgoni, B.; Rizzuto, G.; Libert, C.; Poli, V. Essential role of STAT3 in the control of the acute-phase response as revealed by inducible gene inactivation [correction of activation] in the liver. Mol. Cell Biol. 2001, 21, 1621-1632.
39. Levy, D.E.; Lee, C. What does Stat3 do? J. Clin. Investig. 2002, 109, 1143-1148.
40. Fagard, R.; Metelev, V.; Souissi, I.; Baran-Marszak, F. STAT3 inhibitors for cancer therapy: Have all roads been explored? JAK-STAT 2013, 2, e22882.
41. Ilaria, R.L., Jr.; van Etten, R.A. P210 and P190(BCR/ABL) induce the tyrosine phosphorylation and DNA binding activity of multiple specific STAT family members. J. Biol. Chem. 1996, 271, 31704-31710.
42. Shuai, K.; Halpern, J.; ten Hoeve, J.; Rao, X.; Sawyers, C.L. Constitutive activation of STAT5 by the BCR-ABL oncogene in chronic myelogenous leukemia. Oncogene 1996, 13, 247-254.
43. Steelman, L.S.; Pohnert, S.C.; Shelton, J.G.; Franklin, R.A.; Bertrand, F.E.; McCubrey, J.A. JAK/STAT, Raf/MEK/ERK, PI3K/Akt and BCR-ABL in cell cycle progression and leukemogenesis. Leukemia 2004, 18, 189-218.
44. Spiekermann, K.; Pau, M.; Schwab, R.; Schmieja, K.; Franzrahe, S.; Hiddemann, W. Constitutive activation of STAT3 and STAT5 is induced by leukemic fusion proteins with protein tyrosine kinase activity and is sufficient for transformation of hematopoietic precursor cells. Exp. Hematol. 2002, 30, 262-271.
45. Aggarwal, B.B.; Kunnumakkara, A.B.; Harikumar, K.B.; Gupta, S.R.; Tharakan, S.T.; Koca, C.; Dey, S.; Sung, B. Signal transducer and activator of transcription-3, inflammation, and cancer: How intimate is the relationship? Ann. NY Acad. Sci. 2009, 1171, 59-76.
46. Bromberg, J.F.; Wrzeszczynska, M.H.; Devgan, G.; Zhao, Y.; Pestell, R.G.; Albanese, C.; Darnell, J.E. Stat3 as an oncogene. Cell 1999, 98, 295-303.
47. Levy, D.E.; Inghirami, G. STAT3: A multifaceted oncogene. Proc. Natl. Acad. Sci. USA 2006, 103, 10151-10152.
48. Ishida, Y.; Kondo, T.; Takayasu, T.; Iwakura, Y.; Mukaida, N. The essential involvement of cross-talk between IFN-gamma and TGF-beta in the skin wound-healing process. J. Immunol. 2004, 172, 1848-1855.
49. Shinozaki, M.; Okada, Y.; Kitano, A.; Ikeda, K.; Saika, S.; Shinozaki, M. Impaired cutaneous wound healing with excess granulation tissue formation in TNFalpha-null mice. Arch. Dermatol. Res. 2009, 301, 531-537.
50. Schall, T.J.; Bacon, K.; Toy, K.J.; Goeddel, D.V. Selective attraction of monocytes and T lymphocytes of the memory phenotype by cytokine RANTES. Nature 1990, 347, 669-671.
51. Allavena, P.; Germano, G.; Marchesi, F.; Mantovani, A. Chemokines in cancer related inflammation. Exp. Cell Res. 2011, 317, 664-673.
52. Taub, D.D.; Sayers, T.J.; Carter, C.R.; Ortaldo, J.R. Alpha and beta chemokines induce NK cell migration and enhance NK-mediated cytolysis. J. Immunol. 1995, 155, 3877-3888.
53. Ming, W.J.; Bersani, L.; Mantovani, A. Tumor necrosis factor is chemotactic for monocytes and polymorphonuclear leukocytes. J. Immunol. 1987, 138, 1469-1474.
54. Vivier, E.; Raulet, D.H.; Moretta, A.; Caligiuri, M.A.; Zitvogel, L.; Lanier, L.L.; Yokoyama, W.M.; Ugolini, S. Innate or adaptive immunity? The example of natural killer cells. Science 2011, 331, 44-49.
55. Orr, M.T.; Lanier, L.L. Natural killer cell education and tolerance. Cell 2010, 142, 847-856.
56. Koch, J.; Steinle, A.; Watzl, C.; Mandelboim, O. Activating natural cytotoxicity receptors of natural killer cells in cancer and infection. Trends Immunol. 2013, 34, 182-191.
57. Kovanen, P.E.; Leonard, W.J. Cytokines and immunodeficiency diseases: Critical roles of the gamma(c)-dependent cytokines interleukins 2, 4, 7, 9, 15, and 21, and their signaling pathways. Immunol. Rev. 2004, 202, 67-83.
58. Putz, E.M.; Gotthardt, D.; Hoermann, G.; Csiszar, A.; Wirth, S.; Berger, A.; Straka, E.; Rigler, D.; Wallner, B.; Jamieson, A.M., et al. CDK8-mediated STAT1-S727 phosphorylation restrains NK cell cytotoxicity and tumor surveillance. Cell Rep. 2013, 4, 437-444.
59. Zebedin, E.; Simma, O.; Schuster, C.; Putz, E.M.; Fajmann, S.; Warsch, W.; Eckelhart, E.; Stoiber, D.; Weisz, E.; Schmid, J.A., et al. Leukemic challenge unmasks a requirement for PI3Kdelta in NK cell-mediated tumor surveillance. Blood 2008, 112, 4655-4664.
60. Yu, H.; Kortylewski, M.; Pardoll, D. Crosstalk between cancer and immune cells: Role of STAT3 in the tumour microenvironment. Nat. Rev. Immunol. 2007, 7, 41-51.
61. Wang, T.; Niu, G.; Kortylewski, M.; Burdelya, L.; Shain, K.; Zhang, S.; Bhattacharya, R.; Gabrilovich, D.; Heller, R.; Coppola, D., et al. Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumor cells. Nat. Med. 2004, 10, 48-54.
62. Kühn, R.; Schwenk, F.; Aguet, M.; Rajewsky, K. Inducible gene targeting in mice. Science 1995, 269, 1427-1429.
63. Cao, X.; Shores, E.W.; Hu-Li, J.; Anver, M.R.; Kelsall, B.L.; Russell, S.M.; Drago, J.; Noguchi, M.; Grinberg, A.; Bloom, E.T., et al. Defective lymphoid development in mice lacking expression of the common cytokine receptor gamma chain. Immunity 1995, 2, 223-238.
64. Schreiber, E.; Matthias, P.; Müller, M.M.; Schaffner, W. Rapid detection of octamer binding proteins with -mini-extracts{norm of matrix}, prepared from a small number of cells. Nucleic Acids Res. 1989, 17, 6419.
65. Hoelbl, A.; Kovacic, B.; Kerenyi, M.A.; Simma, O.; Warsch, W.; Cui, Y.; Beug, H.; Hennighausen, L.; Moriggl, R.; Sexl, V. Clarifying the role of Stat5 in lymphoid development and Abelson-induced transformation. Blood 2006, 107, 4898-4906.