Targeted blockade of JAK/STAT3 signaling inhibits ovarian carcinoma growth

Molecular Cancer Therapeutics

Volumn 14, Issue 4, 2015, Pages 1035-1047

  Gritsina, Galina ^a   Xiao, Fang ^a   O'Brien, Shane W ^a   Gabbasov, Rashid ^a,b   Maglaty, Marisa A ^a   Xu, Ren Huan ^a   Thapa, Roshan J ^a   Zhou, Yan ^a   Nicolas, Emmanuelle ^a   Litwin, Samuel ^a   Balachandran, Siddharth ^a   Sigal, Luis J ^a   Huszar, Dennis ^c   Connolly, Denise C ^a  

^a FOX CHASE CANCER CENTER   (United States)

^b KAZAN FEDERAL UNIVERSITY   (Russian Federation)

^c ASTRAZENECA   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

5 CHLORO N2 [1 (5 FLUORO 2 PYRIMIDINYL)ETHYL] N4 (5 METHYL 1H PYRAZOL 3 YL) 2,4 PYRIMIDINEDIAMINE; JANUS KINASE; MATRIX METALLOPROTEINASE; STAT3 PROTEIN; ANALGESIC AGENT; PYRAZOLE DERIVATIVE; PYRIMIDINE DERIVATIVE; VITRONECTIN RECEPTOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; ASCITES; CANCER GROWTH; CARCINOMA CELL; CELL ADHESION; CELL MIGRATION; CELL POPULATION; CELL PROLIFERATION; CELL VIABILITY; CONTROLLED STUDY; DNA BINDING; ENZYME ACTIVITY; FEMALE; GENE EXPRESSION; GROWTH RATE; HUMAN; HUMAN CELL; IMMUNOCOMPETENT CELL; IN VITRO STUDY; MALE; MOUSE; NONHUMAN; OVARY CARCINOMA; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; SUPPRESSOR CELL; TRANSGENIC MOUSE; TUMOR GROWTH; TUMOR MICROENVIRONMENT; TUMOR VOLUME; ANIMAL; CELL MOTION; CELL SURVIVAL; CLUSTER ANALYSIS; DISEASE MODEL; DRUG EFFECTS; DRUG SCREENING; GENE EXPRESSION PROFILING; GENETICS; METABOLISM; OVARIAN NEOPLASMS; PATHOLOGY; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

ANALGESICS; ANIMALS; APOPTOSIS; CELL LINE, TUMOR; CELL MOVEMENT; CELL PROLIFERATION; CELL SURVIVAL; CLUSTER ANALYSIS; DISEASE MODELS, ANIMAL; FEMALE; GENE EXPRESSION; GENE EXPRESSION PROFILING; HUMANS; INTEGRIN ALPHAVBETA3; JANUS KINASES; MATRIX METALLOPROTEINASES; MICE; MICE, TRANSGENIC; OVARIAN NEOPLASMS; PYRAZOLES; PYRIMIDINES; SIGNAL TRANSDUCTION; STAT3 TRANSCRIPTION FACTOR; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84982179890     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-14-0800     Document Type: Article

References (58)

1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics. CA Cancer J Clin 2014;64: 9-29.
2. TCGA. Integrated genomic analyses of ovarian carcinoma. Nature 2011;474:609-15.
3. Liu H, Xiao F, Serebriiskii IG, O'Brien SW, Maglaty MA, Astsaturov I, et al. Network analysis identifies an HSP90-central hub susceptible in ovarian cancer. Clin Cancer Res 2013;19:5053-67.
4. Gao SP, Bromberg JF. Touched and moved by STAT3. Sci STKE 2006;2006: pe30.
5. Avalle L, Pensa S, Regis G, Novelli F, Poli V. STAT1 and STAT3 in tumorigenesis: a matter of balance. JAKSTAT 2012;1:65-72.
6. Chang Q, Bournazou E, Sansone P, Berishaj M,Gao SP, Daly L, et al. The IL-6/JAK/Stat3 feed-forward loop drives tumorigenesis and metastasis. Neoplasia 2013;15:848-62.
7. Silver DL, NaoraH, Liu J, Cheng W, Montell DJ. Activated signal transducer and activator of transcription (STAT) 3: localization in focal adhesions and function in ovarian cancer cell motility. Cancer Res 2004;64:3550-8.
8. Akira S. Roles of STAT3 defined by tissue-specific gene targeting. Oncogene 2000;19:2607-11.
9. Duan Z, Foster R, Bell DA, Mahoney J, Wolak K, Vaidya A, et al. Signal transducers and activators of transcription 3 pathway activation in drugresistant ovarian cancer. Clin Cancer Res 2006;12:5055-63.
10. Huang M, Page C, Reynolds RK, Lin J. Constitutive activation of stat 3 oncogene product in human ovarian carcinoma cells. Gynecol Oncol 2000;79:67-73.
11. Kryczek I, Grybos M, Karabon L, Klimczak A, Lange A. IL-6 production in ovarian carcinoma is associated with histiotype and biological characteristics of the tumour and influences local immunity. Br J Cancer 2000;82:621-8.
12. Nilsson MB, Langley RR, Fidler IJ. Interleukin-6, secreted by human ovarian carcinoma cells, is a potent proangiogenic cytokine. Cancer Res 2005; 65:10794-800.
13. Bollrath J, Phesse TJ, von Burstin VA, Putoczki T, Bennecke M, Bateman T, et al. gp130-mediated Stat3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis. Cancer Cell 2009;15:91-102.
14. Grivennikov S, Karin E, Terzic J, Mucida D, Yu GY, Vallabhapurapu S, et al. IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer. Cancer Cell 2009;15:103-13.
15. KortylewskiM, Swiderski P, Herrmann A, Wang L, Kowolik C, Kujawski M, et al. In vivo delivery of siRNA to immune cells by conjugation to a TLR9 agonist enhances antitumor immune responses. Nat Biotechnol 2009; 27:925-32.
16. Hedvat M, Huszar D, Herrmann A, Gozgit JM, Schroeder A, Sheehy A, et al. The JAK2 inhibitor AZD1480 potently blocks Stat3 signaling and oncogenesis in solid tumors. Cancer Cell 2009;16:487-97.
17. Kortylewski M, Kujawski M, Wang T, Wei S, Zhang S, Pilon-Thomas S, et al. Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity. Nat Med 2005;11:1314-21.
18. Yue P, Turkson J. Targeting STAT3 in cancer: how successful are we? Expert Opin Investig Drugs 2009;18:45-56.
19. Sen M, Thomas SM, Kim S, Yeh JI, Ferris RL, Johnson JT, et al. Firstin-human trial of a STAT3 decoy oligonucleotide in head and neck tumors: implications for cancer therapy. Cancer Discov 2012;2: 694-705.
20. Xin H, Herrmann A, Reckamp K, Zhang W, Pal S, Hedvat M, et al. Antiangiogenic and antimetastatic activity of JAK inhibitor AZD1480. Cancer Res 2011;71:6601-10.
21. Gu L, Talati P, Vogiatzi P, Romero-Weaver AL, Abdulghani J, Liao Z, et al. Pharmacologic suppression of JAK1/2 by JAK1/2 inhibitor AZD1480 potently inhibits IL-6-induced experimental prostate cancer metastases formation. Mol Cancer Ther 2014;13:1246-58.
22. Katsha A, Arras J, Soutto M, Belkhiri A, El-Rifai W. AURKA regulates JAK2-STAT3 activity in human gastric and esophageal cancers. Mol Oncol 2014;8:1419-28.
23. Lee JH, Park KS, Alberobello AT, Kallakury B, Weng MT, Wang Y, et al. The Janus kinases inhibitor AZD1480 attenuates growth of small cell lung cancers in vitro and in vivo. Clin Cancer Res 2013;19:6777-86.
24. McFarland BC, Ma JY, Langford CP, Gillespie GY, Yu H, Zheng Y, et al. Therapeutic potential of AZD1480 for the treatment of human glioblastoma. Mol Cancer Ther 2011;10:2384-93.
25. Stuart E, BuchertM, Putoczki T, Thiem S, Farid R, Elzer J, et al. Therapeutic inhibition of Jak activity inhibits progression of gastrointestinal tumors in mice. Mol Cancer Ther 2014;13:468-74.
26. Connolly DC, Bao R, Nikitin A.Y., Stephens K.C., Poole T.W., Hua X., Harris S.S, Vanderhyden B.C.,Hamilton T.C. Female mice chimeric for expression of the SV40 TAg under control of the MISIIR promoter develop epithelial ovarian cancer. Cancer Research 2003;63:1389-97.
27. Hensley H, Quinn BA, Wolf RL, Litwin SL, Mabuchi S, Williams SJ, et al. Magnetic resonance imaging for detection and determination of tumor volume in a genetically engineered mouse model of ovarian cancer. Cancer Biol Ther 2007;6:1717-25.
28. Connolly DC, Hensley HH. Xenograft and transgenic mouse models of epithelial ovarian cancer and non invasive imaging modalities to monitor ovarian tumor growth in situ-applications in evaluating novel therapeutic agents. Curr Protoc Pharmacol 2009;45:14.12.1-14.12.26.
29. Do TV, Xiao F, Bickel LE, Klein-Szanto AJ, Pathak HB, Hua X, et al. Aurora kinase A mediates epithelial ovarian cancer cell migration and adhesion. Oncogene 2014;33:539-49.
30. Thapa RJ, Basagoudanavar SH, Nogusa S, Irrinki K, Mallilankaraman K, Slifker MJ, et al. NF-kappaB protects cells from gamma interferon-induced RIP1-dependent necroptosis. Mol Cell Biol 2011;31:2934-46.
31. Hensley HH, Roder NA, O'Brien SW, Bickel LE, Xiao F, Litwin S, et al. Combined in vivo molecular and anatomic imaging for detection of ovarian carcinoma-associated protease activity and integrin expression in mice. Neoplasia 2012;14:451-62.
32. Bolstad BM, Irizarry RA, Åstrand M, Speed TP. A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 2003;19:185-93.
33. Smyth GK. Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 2004;3:Article3.
34. Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, et al. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 2004;5:R80.
35. Johnson G, Nour A, Nolan T, Huggett J, Bustin S. Minimum information necessary for quantitative real-time PCR experiments. In:Biassoni R, Raso A, editors. Quantitative real-time PCR. Springer: New York; 2014. p. 5-17.
36. Burke WM, Jin X, Lin HJ, Huang M, Liu R, Reynolds RK, et al. Inhibition of constitutively active Stat3 suppresses growth of human ovarian and breast cancer cells. Oncogene 2001;20:7925-34.
37. Savarese TM, Campbell CL, McQuain C, Mitchell K, Guardiani R, Quesenberry PJ, et al. Coexpression of oncostatin M and its receptors and evidence for STAT3 activation in human ovarian carcinomas. Cytokine 2002;17:324-34.
38. Tan DS, Agarwal R, Kaye SB. Mechanisms of transcoelomic metastasis in ovarian cancer. The Lancet Oncology 2006;7:925-34.
39. Colomiere M, Ward AC, Riley C, Trenerry MK, Cameron-Smith D, Findlay J, et al. Cross talk of signals between EGFR and IL-6R through JAK2/STAT3 mediate epithelial-mesenchymal transition in ovarian carcinomas. Br J Cancer 2009;100:134-44.
40. Vultur A, Arulanandam R, Turkson J, Niu G, Jove R, Raptis L. Stat3 is required for full neoplastic transformation by the Simian Virus 40 large tumor antigen. Mol Biol Cell 2005;16:3832-46.
41. Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C, et al. Stat3 as an oncogene. Cell 1999;98:295-303.
42. Dauer DJ, Ferraro B, Song L, Yu B, Mora L, Buettner R, et al. Stat3 regulates genes common to both wound healing and cancer. Oncogene 2005;24:3397-408.
43. Beck V, Herold H, Benge A, Luber B, Hutzler P, Tschesche H, et al. ADAM15 decreases integrin alphavbeta3/vitronectin-mediated ovarian cancer cell adhesion and motility in an RGD-dependent fashion. Int J Biochem Cell Biol 2005;37:590-603.
44. Landen CN, Kim TJ, Lin YG, Merritt WM, Kamat AA, Han LY, et al. Tumorselective response to antibody-mediated targeting of alphavbeta3 integrin in ovarian cancer. Neoplasia 2008;10:1259-67.
45. Leroy-Dudal J, Demeilliers C, Gallet O, Pauthe E, Dutoit S, Agniel R, et al. Transmigration of human ovarian adenocarcinoma cells through endothelial extracellular matrix involves alphav integrins and the participation of MMP2. Int J Cancer 2005;114:531-43.
46. Schmalfeldt B, Prechtel D, Harting K, Spathe K, Rutke S, Konik E, et al. Increased expression of matrix metalloproteinases (MMP)-2, MMP-9, and the urokinase-type plasminogen activator is associated with progression from benign to advanced ovarian cancer. Clin Cancer Res 2001;7:2396-404.
47. Landen CN, Lin YG, ArmaizPena GN, Das PD, Arevalo JM, Kamat AA, et al. Neuroendocrine modulation of signal transducer and activator of transcription-3 in ovarian cancer. Cancer Res 2007; 67:10389-96.
48. Seo J-M, Park S, Kim J-H. Leukotriene B4 receptor-2 promotes invasiveness and metastasis of ovarian cancer cells through signal transducer and activator of transcription 3 (STAT3)-dependent up-regulation of matrix metalloproteinase 2. J Biol Chem 2012;287:13840-9.
49. Xie T-x, WeiD, LiuM,Gao AC, Ali-Osman F, Sawaya R, et al. Stat3 activation regulates the expression ofmatrix metalloproteinase-2 and tumor invasion and metastasis. Oncogene 2004;23:3550-60.
50. 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.
51. Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer 2009;9:798-809.
52. Vaughan S, Coward JI, Bast RC Jr, Berchuck A, Berek JS, Brenton JD, et al. Rethinking ovarian cancer: recommendations for improving outcomes. Nat Rev Cancer 2011;11:719-25.
53. Wen W, Liang W, Wu J, Kowolik CM, Buettner R, Scuto A, et al. Targeting JAK1/STAT3 signaling suppresses tumor progression and metastasis in a peritoneal model of human ovarian cancer. Mol Cancer Ther 2014;13: 3037-48.
54. Vaidyanathan G, Cismowski MJ, Wang G, Vincent TS, Brown KD, Lanier SM. The Ras-related protein AGS1/RASD1 suppresses cell growth. Oncogene 2004;23:5858-63.
55. Davidson B, Trope CG, Reich R. The role of the tumor stroma in ovarian cancer. Front Oncol 2014;4:104.
56. Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 2004;10:942-9.
57. Facciabene A, Motz GT, Coukos G. T-regulatory cells: key players in tumor immune escape and angiogenesis. Cancer Res 2012;72:2162-71.
58. Harada D, Takigawa N, Kiura K. The role of STAT3 in non-small cell lung cancer. Cancers (Basel) 2014;6:708-22.