Gp130: A promising drug target for cancer therapy

Expert Opinion on Therapeutic Targets

Volumn 17, Issue 11, 2013, Pages 1303-1328

  Xu, Shili ^a   Neamati, Nouri ^a  

^a UNIVERSITY OF MICHIGAN   (United States)

Author keywords

Cancer; Cytokines; Gp130; Signal transduction

Indexed keywords

ALX 0061; C 326; CALCIUM CALMODULIN DEPENDENT PROTEIN KINASE II; CISPLATIN; CLAZAKIZUMAB; DAB 389 INTERLEUKIN 6; DEXAMETHASONE; ETOPOSIDE; FE 999301; GLYCOPROTEIN GP 130; GLYCOPROTEIN P INHIBITOR; INTERLEUKIN 6; JANUS KINASE 2 INHIBITOR; MAR 003US; MEDI 5117; MESSENGER RNA; OLOKIZUMAB; PACLITAXEL; PF 04236921; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PLASMINOGEN ACTIVATOR INHIBITOR 1; PROTEIN KINASE B INHIBITOR; PROTEIN TYROSINE PHOSPHATASE; SARILUMAB; SC 144; SILTUXIMAB; SIRUKUMAB; SMALL MOLECULE TRANSPORT AGENT; SUPPRESSOR OF CYTOKINE SIGNALING; TOCILIZUMAB; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ACUTE GRANULOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC LEUKEMIA; AMINO ACID SUBSTITUTION; ANGIOFOLLICULAR LYMPH NODE HYPERPLASIA; ANGIOGENESIS; ANKYLOSING SPONDYLITIS; APOPTOSIS; ASTROCYTE; BONE MARROW; BRAIN TUMOR; BREAST CANCER; CACHEXIA; CANCER GROWTH; CANCER THERAPY; CARCINOGENESIS; CELL CYCLE PROGRESSION; CELL SURVIVAL; CELLULAR DISTRIBUTION; COLORECTAL CANCER; CROHN DISEASE; CYTOKINE RELEASE; DATA BASE; DIMERIZATION; DRUG TARGETING; ENTERITIS; ENZYME ACTIVATION; FATIGUE; GAIN OF FUNCTION MUTATION; GLEASON SCORE; GLIOBLASTOMA; GLIOMA; HEMATOPOIESIS; KAPOSI SARCOMA; KIDNEY CARCINOMA; LEUKEMIA; LUNG CANCER; LUPUS ERYTHEMATOSUS NEPHRITIS; MACROPHAGE; MALIGNANT MESOTHELIOMA; MELANOMA; MONOCYTE; MULTIPLE CANCER; MULTIPLE MYELOMA; MYELODYSPLASTIC SYNDROME; MYELOMA; MYELOMA CELL; NATIONAL HEALTH ORGANIZATION; NUCLEAR MAGNETIC RESONANCE; OPTICAL RESOLUTION; ORAL MUCOSITIS; OVARY CANCER; PANCREAS ADENOMA; PATHOPHYSIOLOGY; PATIENT SELECTION; PROSTATE BIOPSY; PROSTATE CANCER; PROSTATE CARCINOMA; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN STRUCTURE; PSORIATIC ARTHRITIS; REGULATORY MECHANISM; REVIEW; RHEUMATOID ARTHRITIS; SARCOMA; SEQUENCE ALIGNMENT; SIGNAL TRANSDUCTION; SOLID TUMOR; STOMACH CANCER; SYSTEMIC LUPUS ERYTHEMATOSUS; SYSTEMIC SCLEROSIS; T LYMPHOCYTE; TREATMENT DURATION; X RAY DIFFRACTION;

CYTOKINE RECEPTOR GP130; HUMANS; NEOPLASMS; PROTEIN CONFORMATION; SIGNAL TRANSDUCTION;

EID: 84886882248     PISSN: 14728222     EISSN: 17447631     Source Type: Journal    
DOI: 10.1517/14728222.2013.830105     Document Type: Review

References (223)

1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144:646-74
2. Andersson LC, Gahmberg CG, Kimura AK, et al. Activated human T lymphocytes display new surface glycoproteins. Proc Natl Acad Sci USA 1978;75:3455-8
3. Taga T, Hibi M, Hirata Y, et al. Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. Cell 1989;58:573-81
4. Hibi M, Murakami M, Saito M, et al. Molecular cloning and expression of an IL-6 signal transducer, gp130. Cell 1990;63:1149-57
5. Yin T, Taga T, Tsang ML, et al. Involvement of IL-6 signal transducer gp130 in IL-11-mediated signal transduction. J Immunol 1993;151:2555-61
6. Pflanz S, Hibbert L, Mattson J, et al. WSX-1 and glycoprotein 130 constitute a signal-transducing receptor for IL-27. J Immunol 2004;172:2225-31
7. Ip NY, Nye SH, Boulton TG, et al. CNTF and LIF act on neuronal cells via shared signaling pathways that involve the IL-6 signal transducing receptor component gp130. Cell 1992;69:1121-32
8. Gearing DP, Comeau MR, Friend DJ, et al. The IL-6 signal transducer, gp130: an oncostatin M receptor and affinity converter for the LIF receptor. Science 1992;255:1434-7
9. Pennica D, Shaw KJ, Swanson TA, et al. Cardiotrophin-1. Biological activities and binding to the leukemia inhibitory factor receptor/gp130 signaling complex. J Biol Chem 1995;270:10915-22
10. Elson GC, Lelievre E, Guillet C, et al. CLF associates with CLC to form a functional heteromeric ligand for the CNTF receptor complex. Nat Neurosci 2000;3:867-72
11. Derouet D, Rousseau F, Alfonsi F, et al. Neuropoietin, a new IL-6-related cytokine signaling through the ciliary neurotrophic factor receptor. Proc Natl Acad Sci USA 2004;101:4827-32
12. Osborne J, Moore PS, Chang Y. KSHV-encoded viral IL-6 activates multiple human IL-6 signaling pathways. Hum Immunol 1999;60:921-7
13. Kaleeba JA, Bergquam EP, Wong SW. A rhesus macaque rhadinovirus related to Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 encodes a functional of interleukin-6. J Virol 1999;73:6177-81
14. Matadeen R, Hon WC, Heath JK, et al. The dynamics of signal triggering in a gp130-receptor complex. Structure 2007;15:441-8
15. Skiniotis G, Boulanger MJ, Garcia KC, et al. Signaling conformations of the tall cytokine receptor gp130 when in complex with IL-6 and IL-6 receptor. Nat Struct Mol Biol 2005;12:545-51
16. Wang X, Lupardus P, Laporte SL, et al. Structural biology of shared cytokine receptors. Annu Rev Immunol 2009;27:29-60
17. Narazaki M, Yasukawa K, Saito T, et al. Soluble forms of the interleukin-6 signal-transducing receptor component gp130 in human serum possessing a potential to inhibit signals through membrane-anchored gp130. Blood 1993;82:1120-6
18. Zhang JG, Zhang Y, Owczarek CM, et al. Identification and characterization of two distinct truncated forms of gp130 and a soluble form of leukemia inhibitory factor receptor alpha-chain in normal human urine and plasma. J Biol Chem 1998;273:10798-805
19. Tanaka M, Kishimura M, Ozaki S, et al. Cloning of novel soluble gp130 and detection of its neutralizing autoantibodies in rheumatoid arthritis. J Clin Invest 2000;106:137-44
20. Mitsuyama K, Tomiyasu N, Suzuki A, et al. A form of circulating interleukin-6 receptor component soluble gp130 as a potential interleukin-6 inhibitor in inflammatory bowel disease. Clin Exp Immunol 2006;143:125-31
21. Richards PJ, Nowell MA, Horiuchi S, et al. Functional characterization of a soluble gp130 isoform and its therapeutic capacity in an experimental model of inflammatory arthritis. Arthritis Rheum 2006;54:1662-72
22. Boulanger MJ, Garcia KC. Shared cytokine signaling receptors: structural insights from the gp130 system. Adv Protein Chem 2004;68:107-46
23. Sims NA. gp130 signaling in bone cell biology: multiple roles revealed by analysis of genetically altered mice. Mol Cell Endocrinol 2009;310:30-9
24. Traum D, Timothee P, Silver J, et al. IL-10-induced gp130 expression in mouse mast cells permits IL-6 trans-signaling. J Leukoc Biol 2012;91:427-35
25. Xu S, Grande F, Garofalo A, et al. Discovery of a novel orally active small-molecule gp130 inhibitor for the treatment of ovarian cancer. Mol Cancer Ther 2013;12:937-49
26. Bonito NA, Drechsler J, Stoecker S, et al. Control of gp130 expression by the mitogen-activated protein kinase ERK2. Oncogene 2013; [Epub ahead of print]
27. O'Brien CA, Manolagas SC. Isolation and characterization of the human gp130 promoter. Regulation by STATS. J Biol Chem 1997;272:15003-10
28. Waetzig GH, Chalaris A, Rosenstiel P, et al. N-linked glycosylation is essential for the stability but not the signaling function of the interleukin-6 signal transducer glycoprotein 130. J Biol Chem 2010;285:1781-9
29. Gibson RM, Schiemann WP, Prichard LB, et al. Phosphorylation of human gp130 at Ser-782 adjacent to the Di-leucine internalization motif. Effects on expression and signaling. J Biol Chem 2000;275:22574-82
30. Radtke S, Wuller S, Yang XP, et al. Cross-regulation of cytokine signalling: pro-inflammatory cytokines restrict IL-6 signalling through receptor internalisation and degradation. J Cell Sci 2010;123:947-59
31. Gibson RM, Laszlo GS, Nathanson NM. Calmodulin-dependent protein kinases phosphorylate gp130 at the serine-based dileucine internalization motif. Biochim Biophys Acta 2005;1714:56-62
32. Mitsuhashi S, Shima H, Tanuma N, et al. Protein phosphatase type 2A, PP2A, is involved in degradation of gp130. Mol Cell Biochem 2005;269:183-7
33. Tanaka Y, Tanaka N, Saeki Y, et al. c-Cbl-dependent monoubiquitination and lysosomal degradation of gp130. Mol Cell Biol 2008;28:4805-18
34. Graf D, Haselow K, Munks I, et al. Caspase-mediated cleavage of the signal-transducing IL-6 receptor subunit gp130. Arch Biochem Biophys 2008;477:330-8
35. Thiel S, Behrmann I, Dittrich E, et al. Internalization of the interleukin 6 signal transducer gp130 does not require activation of the Jak/STAT pathway. Biochem J 1998;330(Pt 1):47-54
36. Johnson C, Han Y, Hughart N, et al. Interleukin-6 and its receptor, key players in hepatobiliary inflammation and cancer. Transl Gastroint Cancer 2012;1:58-70
37. Febbraio MA. gp130 receptor ligands as potential therapeutic targets for obesity. J Clin Invest 2007;117:841-9
38. Silver JS, Hunter CA. gp130 at the nexus of inflammation, autoimmunity, and cancer. J Leukoc Biol 2010;88:1145-56
39. Debnath B, Xu S, Neamati N. Small molecule inhibitors of signal transducer and activator of transcription 3 (Stat3) protein. J Med Chem 2012;55:6645-68
40. Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer 2009;9:798-809
41. Jones SA, Scheller J, Rose-John S. Therapeutic strategies for the clinical blockade of IL-6/gp130 signaling. J Clin Invest 2011;121:3375-83
42. Scheller J, Chalaris A, Schmidt-Arras D, et al. The pro-and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta 2011;1813:878-88
43. Regis G, Pensa S, Boselli D, et al. Ups and downs: the STAT1:STAT3 seesaw of interferon and gp130 receptor signalling. Semin Cell Dev Biol 2008;19:351-9
44. Haan S, Keller JF, Behrmann I, et al. Multiple reasons for an inefficient STAT1 response upon IL-6-type cytokine stimulation. Cell Signal 2005;17:1542-50
45. Cheon H, Yang J, Stark GR. The functions of signal transducers and activators of transcriptions 1 and 3 as cytokine-inducible proteins. J Interferon Cytokine Res 2011;31:33-40
46. Vivanco I, Sawyers CL. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer 2002;2:489-501
47. Kolch W, Kotwaliwale A, Vass K, et al. The role of Raf kinases in malignant transformation. Expert Rev Mol Med 2002;4:1-18
48. Yamamoto T, Sekine Y, Kashima K, et al. The nuclear isoform of protein-tyrosine phosphatase TC-PTP regulates interleukin-6-mediated signaling pathway through STAT3 dephosphorylation. Biochem Biophys Res Commun 2002;297:811-17
49. Muromoto R, Sekine Y, Imoto S, et al. BART is essential for nuclear retention of STAT3. Int Immunol 2008;20:395-403
50. Herrmann A, Vogt M, Monnigmann M, et al. Nucleocytoplasmic shuttling of persistently activated STAT3. J Cell Sci 2007;120:3249-61
51. Eiken HG, Oie E, Damas JK, et al. Myocardial gene expression of leukaemia inhibitory factor, interleukin-6 and glycoprotein 130 in end-stage human heart failure. Eur J Clin Invest 2001;31:389-97
52. Freed DH, Moon MC, Borowiec AM, et al. Cardiotrophin-1: expression in experimental myocardial infarction and potential role in post-MI wound healing. Mol Cell Biochem 2003;254:247-56
53. Butcher BA, Kim L, Panopoulos AD, et al. IL-10-independent STAT3 activation by Toxoplasma gondii mediates suppression of IL-12 and TNF-alpha in host macrophages. J Immunol 2005;174:3148-52
54. Naka T, Narazaki M, Hirata M, et al. Structure and function of a new STAT-induced STAT inhibitor. Nature 1997;387:924-9
55. Stephanou A, Brar B, Heads R, et al. Cardiotrophin-1 induces heat shock protein accumulation in cultured cardiac cells and protects them from stressful stimuli. J Mol Cell Cardiol 1998;30:849-55
56. Tamiya T, Kashiwagi I, Takahashi R, et al. Suppressors of cytokine signaling (SOCS) proteins and JAK/STAT pathways: regulation of T-cell inflammation by SOCS1 and SOCS3. Arterioscler Thromb Vasc Biol 2011;31:980-5
57. Shuai K, Liu B. Regulation of gene-activation pathways by PIAS proteins in the immune system. Nat Rev Immunol 2005;5:593-605
58. Zhang X, Guo A, Yu J, et al. Identification of STAT3 as a substrate of receptor protein tyrosine phosphatase T. Proc Natl Acad Sci USA 2007;104:4060-4
59. Yoshida K, Taga T, Saito M, et al. Targeted disruption of gp130, a common signal transducer for the interleukin 6 family of cytokines, leads to myocardial and hematological disorders. Proc Natl Acad Sci USA 1996;93:407-11
60. Fasnacht N, Muller W. Conditional gp130 deficient mouse mutants. Semin Cell Dev Biol 2008;19:379-84
61. Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 2008;455:1061-8
62. Shai R, Shi T, Kremen TJ, et al. Gene expression profiling identifies molecular subtypes of gliomas. Oncogene 2003;22:4918-23
63. Sun L, Hui AM, Su Q, et al. Neuronal and glioma-derived stem cell factor induces angiogenesis within the brain. Cancer Cell 2006;9:287-300
64. Jones J, Otu H, Spentzos D, et al. Gene signatures of progression and metastasis in renal cell cancer. Clin Cancer Res 2005;11:5730-9
65. Beroukhim R, Brunet JP, Di Napoli A, et al. Patterns of gene expression and copy-number alterations in von-hippel lindau disease-associated and sporadic clear cell carcinoma of the kidney. Cancer Res 2009;69:4674-81
66. Zhan F, Hardin J, Kordsmeier B, et al. Global gene expression profiling of multiple myeloma, monoclonal gammopathy of undetermined significance, and normal bone marrow plasma cells. Blood 2002;99:1745-57
67. Korkola JE, Houldsworth J, Chadalavada RS, et al. Down-regulation of stem cell genes, including those in a 200-kb gene cluster at 12p13.31, is associated with in vivo differentiation of human male germ cell tumors. Cancer Res 2006;66:820-7
68. Compagno M, Lim WK, Grunn A, et al. Mutations of multiple genes cause deregulation of NF-kappaB in diffuse large B-cell lymphoma. Nature 2009;459:717-21
69. Basso K, Margolin AA, Stolovitzky G, et al. Reverse engineering of regulatory networks in human B cells. Nat Genet 2005;37:382-90
70. Lenz G, Wright G, Dave SS, et al. Stromal gene signatures in large-B-cell lymphomas. N Engl J Med 2008;359:2313-23
71. Kovacs E. How does interleukin-6 affect the membrane expressions of interleukin-6 receptor and gp130 and the proliferation of the human myeloma cell line OPM-2? Biomed Pharmacother 2003;57:489-94
72. Cheung WC, Van Ness B. Distinct IL-6 signal transduction leads to growth arrest and death in B cells or growth promotion and cell survival in myeloma cells. Leukemia 2002;16:1182-8
73. Jourdan M, Mahtouk K, Veyrune JL, et al. Delineation of the roles of paracrine and autocrine interleukin-6 (IL-6) in myeloma cell lines in survival versus cell cycle. A possible model for the cooperation of myeloma cell growth factors. Eur Cytokine Netw 2005;16:57-64
74. Gaillard JP, Liautard J, Klein B, et al. Major role of the soluble interleukin-6/interleukin-6 receptor complex for the proliferation of interleukin-6-dependent human myeloma cell lines. Eur J Immunol 1997;27:3332-40
75. Burger R, Neipel F, Fleckenstein B, et al. Human herpesvirus type 8 interleukin-6 homologue is functionally active on human myeloma cells. Blood 1998;91:1858-63
76. Shain KH, Yarde DN, Meads MB, et al. Beta1 integrin adhesion enhances IL-6-mediated STAT3 signaling in myeloma cells: implications for microenvironment influence on tumor survival and proliferation. Cancer Res 2009;69:1009-15
77. Wang YD, De Vos J, Jourdan M, et al. Cooperation between heparin-binding EGF-like growth factor and interleukin-6 in promoting the growth of human myeloma cells. Oncogene 2002;21:2584-92
78. Zhang S, Suvannasankha A, Crean CD, et al. The novel histone deacetylase inhibitor, AR-42, inhibits gp130/Stat3 pathway and induces apoptosis and cell cycle arrest in multiple myeloma cells. Int J Cancer 2011;129:204-13
79. Halimi H, Eisenstein M, Oh JW, et al. Epitope peptides from interleukin-6 receptor which inhibit the growth of human myeloma cells. Eur Cytokine Netw 1995;6:135-43
80. Demartis A, Bernassola F, Savino R, et al. Interleukin 6 receptor superantagonists are potent inducers of human multiple myeloma cell death. Cancer Res 1996;56:4213-18
81. De Vos J, Jourdan M, Tarte K, et al. JAK2 tyrosine kinase inhibitor tyrphostin AG490 downregulates the mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription (STAT) pathways and induces apoptosis in myeloma cells. Br J Haematol 2000;109:823-8
82. Hausherr A, Tavares R, Schaffer M, et al. Inhibition of IL-6-dependent growth of myeloma cells by an acidic peptide repressing the gp130-mediated activation of Src family kinases. Oncogene 2007;26:4987-98
83. Suzuki H, Yasukawa K, Saito T, et al. Anti-human interleukin-6 receptor antibody inhibits human myeloma growth in vivo. Eur J Immunol 1992;22:1989-93
84. Juneja HS, Lee S, Thomazy V, et al. Acute activation of gp130 gene expression in bone marrow stromal cells by contact with myeloma-derived lymphoblastic cell line ARH77 cell membranes. J Interferon Cytokine Res 2001;21:157-66
85. Rodriguez C, Theillet C, Portier M, et al. Molecular analysis of the IL-6 receptor in human multiple myeloma, an IL-6-related disease. FEBS Lett 1994;341:156-61
86. Kyrtsonis MC, Dedoussis G, Zervas C, et al. Soluble interleukin-6 receptor (sIL-6R), a new prognostic factor in multiple myeloma. Br J Haematol 1996;93:398-400
87. Okamoto M, Lee C, Oyasu R. Interleukin-6 as a paracrine and autocrine growth factor in human prostatic carcinoma cells in vitro. Cancer Res 1997;57:141-6
88. Lou W, Ni Z, Dyer K, et al. Interleukin-6 induces prostate cancer cell growth accompanied by activation of stat3 signaling pathway. Prostate 2000;42:239-42
89. Shariat SF, Andrews B, Kattan MW, et al. Plasma levels of interleukin-6 and its soluble receptor are associated with prostate cancer progression and metastasis. Urology 2001;58:1008-15
90. Royuela M, Ricote M, Parsons MS, et al. Immunohistochemical analysis of the IL-6 family of cytokines and their receptors in benign, hyperplasic, and malignant human prostate. J Pathol 2004;202:41-9
91. Kwon EM, Salinas CA, Kolb S, et al. Genetic polymorphisms in inflammation pathway genes and prostate cancer risk. Cancer Epidemiol Biomarkers Prev 2011;20:923-33
92. Zoubeidi A, Rocha J, Zouanat FZ, et al. The Fer tyrosine kinase cooperates with interleukin-6 to activate signal transducer and activator of transcription 3 and promote human prostate cancer cell growth. Mol Cancer Res 2009;7:142-55
93. Liu XH, Kirschenbaum A, Lu M, et al. Prostaglandin E(2) stimulates prostatic intraepithelial neoplasia cell growth through activation of the interleukin-6/GP130/STAT-3 signaling pathway. Biochem Biophys Res Commun 2002;290:249-55
94. Chun JY, Nadiminty N, Dutt S, et al. Interleukin-6 regulates androgen synthesis in prostate cancer cells. Clin Cancer Res 2009;15:4815-22
95. Hafeez BB, Zhong W, Weichert J, et al. Genetic ablation of PKC epsilon inhibits prostate cancer development and metastasis in transgenic mouse model of prostate adenocarcinoma. Cancer Res 2011;71:2318-27
96. Godoy-Tundidor S, Cavarretta IT, Fuchs D, et al. Interleukin-6 and oncostatin M stimulation of proliferation of prostate cancer 22Rv1 cells through the signaling pathways of p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase. Prostate 2005;64:209-16
97. Chung TD, Yu JJ, Kong TA, et al. Interleukin-6 activates phosphatidylinositol-3 kinase, which inhibits apoptosis in human prostate cancer cell lines. Prostate 2000;42:1-7
98. Borsellino N, Bonavida B, Ciliberto G, et al. Blocking signaling through the Gp130 receptor chain by interleukin-6 and oncostatin M inhibits PC-3 cell growth and sensitizes the tumor cells to etoposide and cisplatin-mediated cytotoxicity. Cancer 1999;85:134-44
99. Shariat SF, Chromecki TF, Hoefer J, et al. Soluble gp130 regulates prostate cancer invasion and progression in an interleukin-6 dependent and independent manner. J Urol 2011;186:2107-14
100. Chung TD, Yu JJ, Spiotto MT, et al. Characterization of the role of IL-6 in the progression of prostate cancer. Prostate 1999;38:199-207
101. Schneider MR, Hoeflich A, Fischer JR, et al. Interleukin-6 stimulates clonogenic growth of primary and metastatic human colon carcinoma cells. Cancer Lett 2000;151:31-8
102. Li Y, de Haar C, Chen M, et al. Disease-related expression of the IL6/STAT3/SOCS3 signalling pathway in ulcerative colitis and ulcerative colitis-related carcinogenesis. Gut 2010;59:227-35
103. Grivennikov S, Karin E, Terzic J, 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
104. Bollrath J, Phesse TJ, von Burstin VA, 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
105. Matsumoto S, Hara T, Mitsuyama K, et al. Essential roles of IL-6 trans-signaling in colonic epithelial cells, induced by the IL-6/soluble-IL-6 receptor derived from lamina propria macrophages, on the development of colitis-associated premalignant cancer in a murine model. J Immunol 2010;184:1543-51
106. Becker C, Fantini MC, Schramm C, et al. TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling. Immunity 2004;21:491-501
107. Dowdall JF, Winter DC, Andrews E, et al. Soluble interleukin 6 receptor (sIL-6R) mediates colonic tumor cell adherence to the vascular endothelium: a mechanism for metastatic initiation? J Surg Res 2002;107:1-6
108. Watson JM, Sensintaffar JL, Berek JS, et al. Constitutive production of interleukin 6 by ovarian cancer cell lines and by primary ovarian tumor cultures. Cancer Res 1990;50:6959-65
109. Wang Y, Yang J, Gao Y, et al. Regulatory effect of e2, IL-6 and IL-8 on the growth of epithelial ovarian cancer cells. Cell Mol Immunol 2005;2:365-72
110. Syed V, Ulinski G, Mok SC, et al. Reproductive hormone-induced, STAT3-mediated interleukin 6 action in normal and malignant human ovarian surface epithelial cells. J Natl Cancer Inst 2002;94:617-29
111. Wang Y, Niu XL, Qu Y, et al. Autocrine production of interleukin-6 confers cisplatin and paclitaxel resistance in ovarian cancer cells. Cancer Lett 2010;295:110-23
112. Wang Y, Li L, Guo X, et al. Interleukin-6 signaling regulates anchorage-independent growth, proliferation, adhesion and invasion in human ovarian cancer cells. Cytokine 2012;59:228-36
113. Lo CW, Chen MW, Hsiao M, et al. IL-6 trans-signaling in formation and progression of malignant ascites in ovarian cancer. Cancer Res 2011;71:424-34
114. Plante M, Rubin SC, Wong GY, et al. Interleukin-6 level in serum and ascites as a prognostic factor in patients with epithelial ovarian cancer. Cancer 1994;73:1882-8
115. Scambia G, Testa U, Panici PB, et al. Interleukin-6 serum levels in patients with gynecological tumors. Int J Cancer 1994;57:318-23
116. Tempfer C, Zeisler H, Sliutz G, et al. Serum evaluation of interleukin 6 in ovarian cancer patients. Gynecol Oncol 1997;66:27-30
117. Scambia G, Testa U, Benedetti Panici P, et al. Prognostic significance of interleukin 6 serum levels in patients with ovarian cancer. Br J Cancer 1995;71:354-6
118. Penson RT, Kronish K, Duan Z, et al. Cytokines IL-1beta, IL-2, IL-6, IL-8, MCP-1, GM-CSF and TNFalpha in patients with epithelial ovarian cancer and their relationship to treatment with paclitaxel. Int J Gynecol Cancer 2000;10:33-41
119. Badache A, Hynes NE. Interleukin 6 inhibits proliferation and, in cooperation with an epidermal growth factor receptor autocrine loop, increases migration of T47D breast cancer cells. Cancer Res 2001;61:383-91
120. Selander KS, Li L, Watson L, et al. Inhibition of gp130 signaling in breast cancer blocks constitutive activation of Stat3 and inhibits in vivo malignancy. Cancer Res 2004;64:6924-33
121. Gao SP, Mark KG, Leslie K, et al. Mutations in the EGFR kinase domain mediate STAT3 activation via IL-6 production in human lung adenocarcinomas. J Clin Invest 2007;117:3846-56
122. Fu J, Zheng J, Fang W, et al. Effect of interleukin-6 on the growth of human lung cancer cell line. Chin Med J (Engl) 1998;111:265-8
123. Seike T, Fujita K, Yamakawa Y, et al. Interaction between lung cancer cells and astrocytes via specific inflammatory cytokines in the microenvironment of brain metastasis. Clin Exp Metastasis 2011;28:13-25
124. Haura EB, Livingston S, Coppola D. Autocrine interleukin-6/interleukin-6 receptor stimulation in non-small-cell lung cancer. Clin Lung Cancer 2006;7:273-5
125. Costes V, Liautard J, Picot MC, et al. Expression of the interleukin 6 receptor in primary renal cell carcinoma. J Clin Pathol 1997;50:835-40
126. Blay JY, Schemann S, Favrot MC. Local production of interleukin 6 by renal adenocarcinoma in vivo. J Natl Cancer Inst 1994;86:238
127. Blay JY, Negrier S, Combaret V, et al. Serum level of interleukin 6 as a prognosis factor in metastatic renal cell carcinoma. Cancer Res 1992;52:3317-22
128. Yoshida N, Ikemoto S, Narita K, et al. Interleukin-6, tumour necrosis factor alpha and interleukin-1beta in patients with renal cell carcinoma. Br J Cancer 2002;86:1396-400
129. Dosquet C, Coudert MC, Lepage E, et al. Are angiogenic factors, cytokines, and soluble adhesion molecules prognostic factors in patients with renal cell carcinoma? Clin Cancer Res 1997;3:2451-8
130. Menetrier-Caux C, Montmain G, Dieu MC, et al. Inhibition of the differentiation of dendritic cells from CD34(+) progenitors by tumor cells: role of interleukin-6 and macrophage colony-stimulating factor. Blood 1998;92:4778-91
131. Mizutani Y, Bonavida B, Koishihara Y, et al. Sensitization of human renal cell carcinoma cells to cis-diamminedichloroplatinum (II) by anti-interleukin 6 monoclonal antibody or anti-interleukin 6 receptor monoclonal antibody. Cancer Res 1995;55:590-6
132. Sgadari C, Bacigalupo I, Barillari G, et al. Pharmacological management of Kaposi's sarcoma. Expert Opin Pharmacother 2011;12:1669-90
133. Miles SA, Rezai AR, Salazar-Gonzalez JF, et al. AIDS Kaposi sarcoma-derived cells produce and respond to interleukin 6. Proc Natl Acad Sci USA 1990;87:4068-72
134. Aoki Y, Jaffe ES, Chang Y, et al. Angiogenesis and hematopoiesis induced by Kaposi's sarcoma-associated herpesvirus-encoded interleukin-6. Blood 1999;93:4034-43
135. Murakami-Mori K, Taga T, Kishimoto T, et al. The soluble form of the IL-6 receptor (sIL-6R alpha) is a potent growth factor for AIDS-associated Kaposi's sarcoma (KS) cells; the soluble form of gp130 is antagonistic for sIL-6R alpha-induced AIDS-KS cell growth. Int Immunol 1996;8:595-602
136. Murakami-Mori K, Mori S, Taga T, et al. Enhancement of gp130-mediated tyrosine phosphorylation of STAT3 and its DNA-binding activity in dexamethasone-treated AIDS-associated Kaposi's sarcoma cells: selective synergy between dexamethasone and gp130-related growth factors in Kaposi's sarcoma cell proliferation. J Immunol 1997;158:5518-26
137. Klouche M, Brockmeyer N, Knabbe C, et al. Human herpesvirus 8-derived viral IL-6 induces PTX3 expression in Kaposi's sarcoma cells. AIDS 2002;16:F9-18
138. Suthaus J, Stuhlmann-Laeisz C, Tompkins VS, et al. HHV-8-encoded viral IL-6 collaborates with mouse IL-6 in the development of multicentric Castleman disease in mice. Blood 2012;119:5173-81
139. Masood R, Lunardi-Iskandar Y, Jean LF, et al. Inhibition of AIDS-associated Kaposi's sarcoma cell growth by DAB389-interleukin 6. AIDS Res Hum Retroviruses 1994;10:969-75
140. Rebouissou S, Amessou M, Couchy G, et al. Frequent in-frame somatic deletions activate gp130 in inflammatory hepatocellular tumours. Nature 2009;457:200-4
141. Pilati C, Amessou M, Bihl MP, et al. Somatic mutations activating STAT3 in human inflammatory hepatocellular adenomas. J Exp Med 2011;208:1359-66
142. Maione D, Di Carlo E, Li W, et al. Coexpression of IL-6 and soluble IL-6R causes nodular regenerative hyperplasia and adenomas of the liver. EMBO J 1998;17:5588-97
143. Okamoto M, Hattori K, Oyasu R. Interleukin-6 functions as an autocrine growth factor in human bladder carcinoma cell lines in vitro. Int J Cancer 1997;72:149-54
144. Wang H, Lathia JD, Wu Q, et al. Targeting interleukin 6 signaling suppresses glioma stem cell survival and tumor growth. Stem Cells 2009;27:2393-404
145. Saily M, Koistinen P, Zheng A, et al. Signaling through interleukin-6 receptor supports blast cell proliferation in acute myeloblastic leukemia. Eur J Haematol 1998;61:190-6
146. Chatterjee M, Osborne J, Bestetti G, et al. Viral IL-6-induced cell proliferation and immune evasion of interferon activity. Science 2002;298:1432-5
147. Zhang L, Yang J, Qian J, et al. Role of the microenvironment in mantle cell lymphoma: IL-6 is an important survival factor for the tumor cells. Blood 2012;120:3783-92
148. Adachi Y, Aoki C, Yoshio-Hoshino N, et al. Interleukin-6 induces both cell growth and VEGF production in malignant mesotheliomas. Int J Cancer 2006;119:1303-11
149. Lesina M, Kurkowski MU, Ludes K, et al. Stat3/Socs3 activation by IL-6 transsignaling promotes progression of pancreatic intraepithelial neoplasia and development of pancreatic cancer. Cancer Cell 2011;19:456-69
150. Miyamoto Y, Hosotani R, Doi R, et al. Interleukin-6 inhibits radiation induced apoptosis in pancreatic cancer cells. Anticancer Res 2001;21:2449-56
151. Thiele JO, Lohrer P, Schaaf L, et al. Functional in vitro studies on the role and regulation of interleukin-6 in human somatotroph pituitary adenomas. Eur J Endocrinol 2003;149:455-61
152. Ahmed ST, Darnell JE Jr. Serpin B3/B4, activated by STAT3, promote survival of squamous carcinoma cells. Biochem Biophys Res Commun 2009;378:821-5
153. Giraudo E, Arese M, Toniatti C, et al. IL-6 is an in vitro and in vivo autocrine growth factor for middle T antigen-transformed endothelial cells. J Immunol 1996;157:2618-23
154. Nishimoto N, Ogata A, Shima Y, et al. Oncostatin M, leukemia inhibitory factor, and interleukin 6 induce the proliferation of human plasmacytoma cells via the common signal transducer, gp130. J Exp Med 1994;179:1343-7
155. Okamoto M, Oyasu R. Effect of transfected interleukin-6 in non-tumorigenic and tumorigenic rat urothelial cell lines. Int J Cancer 1996;68:616-21
156. Garbers C, Scheller J. Interleukin-6 and interleukin-11: same but different. Biol Chem 2013;394(9):1145-61
157. Merchant JL. What lurks beneath: IL-11, via Stat3, promotes inflammation-associated gastric tumorigenesis. J Clin Invest 2008;118:1628-31
158. Jackson CB, Judd LM, Menheniott TR, et al. Augmented gp130-mediated cytokine signalling accompanies human gastric cancer progression. J Pathol 2007;213:140-51
159. Putoczki T, Ernst M. More than a sidekick: the IL-6 family cytokine IL-11 links inflammation to cancer. J Leukoc Biol 2010;88:1109-17
160. Nakayama T, Yoshizaki A, Izumida S, et al. Expression of interleukin-11 (IL-11) and IL-11 receptor alpha in human gastric carcinoma and IL-11 upregulates the invasive activity of human gastric carcinoma cells. Int J Oncol 2007;30:825-33
161. Tebbutt NC, Giraud AS, Inglese M, et al. Reciprocal regulation of gastrointestinal homeostasis by SHP2 and STAT-mediated trefoil gene activation in gp130 mutant mice. Nat Med 2002;8:1089-97
162. Howlett M, Judd LM, Jenkins B, et al. Differential regulation of gastric tumor growth by cytokines that signal exclusively through the coreceptor gp130. Gastroenterology 2005;129:1005-18
163. Ernst M, Najdovska M, Grail D, et al. STAT3 and STAT1 mediate IL-11-dependent and inflammation-associated gastric tumorigenesis in gp130 receptor mutant mice. J Clin Invest 2008;118:1727-38
164. Judd LM, Ulaganathan M, Howlett M, et al. Cytokine signalling by gp130 regulates gastric mucosal healing after ulceration and, indirectly, antral tumour progression. J Pathol 2009;217:552-62
165. Thiem S, Pierce TP, Palmieri M, et al. mTORC1 inhibition restricts inflammation-associated gastrointestinal tumorigenesis in mice. J Clin Invest 2013;123:767-81
166. Kimura T, Sakabe H, Minamiguchi H, et al. Interleukin-11 (IL-11) enhances clonal proliferation of acute myelogenous leukemia cells with strong expression of the IL-11 receptor alpha chain and signal transducing gp130. Leukemia 1999;13:1018-27
167. Suman P, Poehlmann TG, Prakash GJ, et al. Interleukin-11 increases invasiveness of JEG-3 choriocarcinoma cells by modulating STAT3 expression. J Reprod Immunol 2009;82:1-11
168. Murphy GM Jr, Bitting L, Majewska A, et al. Expression of interleukin-11 and its encoding mRNA by glioblastoma cells. Neurosci Lett 1995;196:153-6
169. Zhang XG, Gu JJ, Lu ZY, et al. Ciliary neurotropic factor, interleukin 11, leukemia inhibitory factor, and oncostatin M are growth factors for human myeloma cell lines using the interleukin 6 signal transducer gp130. J Exp Med 1994;179:1337-42
170. Campbell CL, Guardiani R, Ollari C, et al. Interleukin-11 receptor expression in primary ovarian carcinomas. Gynecol Oncol 2001;80:121-7
171. Campbell CL, Jiang Z, Savarese DM, et al. Increased expression of the interleukin-11 receptor and evidence of STAT3 activation in prostate carcinoma. Am J Pathol 2001;158:25-32
172. Ren L, Wang X, Dong Z, et al. Bone metastasis from breast cancer involves elevated IL-11 expression and the gp130/STAT3 pathway. Med Oncol 2013;30:634
173. Garcia-Tunon I, Ricote M, Ruiz A, et al. OSM, LIF, its receptors, and its relationship with the malignance in human breast carcinoma (in situ and in infiltrative). Cancer Invest 2008;26:222-9
174. Estrov Z, Samal B, Lapushin R, et al. Leukemia inhibitory factor binds to human breast cancer cells and stimulates their proliferation. J Interferon Cytokine Res 1995;15:905-13
175. Liu J, Hadjokas N, Mosley B, et al. Oncostatin M-specific receptor expression and function in regulating cell proliferation of normal and malignant mammary epithelial cells. Cytokine 1998;10:295-302
176. Lentzsch S, Chatterjee M, Gries M, et al. PI3-K/AKT/FKHR and MAPK signaling cascades are redundantly stimulated by a variety of cytokines and contribute independently to proliferation and survival of multiple myeloma cells. Leukemia 2004;18:1883-90
177. Park JI, Strock CJ, Ball DW, et al. Interleukin-1beta can mediate growth arrest and differentiation via the leukemia inhibitory factor/JAK/STAT pathway in medullary thyroid carcinoma cells. Cytokine 2005;29:125-34
178. Kamohara H, Ogawa M, Ishiko T, et al. Leukemia inhibitory factor functions as a growth factor in pancreas carcinoma cells: involvement of regulation of LIF and its receptor expression. Int J Oncol 2007;30:977-83
179. Zarling JM, Shoyab M, Marquardt H, et al. Oncostatin M: a growth
180. Brown TJ, Lioubin MN, Marquardt H. Purification and characterization of cytostatic lymphokines produced by activated human T lymphocytes. Synergistic antiproliferative activity of transforming growth factor beta 1, interferon-gamma, and oncostatin M for human melanoma cells. J Immunol 1987;139:2977-83
181. Malik N, Kallestad JC, Gunderson NL, et al. Molecular cloning, sequence analysis, and functional expression of a novel growth regulator, oncostatin M. Mol Cell Biol 1989;9:2847-53
182. Kortylewski M, Heinrich PC, Mackiewicz A, et al. Interleukin-6 and oncostatin M-induced growth inhibition of human A375 melanoma cells is STAT-dependent and involves upregulation of the cyclin-dependent kinase inhibitor p27/Kip1. Oncogene 1999;18:3742-53
183. Gibbs P, Chen Q, Robinson WA. Effects of oncostatin M and tamoxifen on human melanoma cells. Melanoma Res 1998;8:221-6
184. Schaefer LK, Menter DG, Schaefer TS. Activation of stat3 and stat1 DNA binding and transcriptional activity in human brain tumour cell lines by gp130 cytokines. Cell Signal 2000;12:143-51
185. Halfter H, Lotfi R, Westermann R, et al. Inhibition of growth and induction of differentiation of glioma cell lines by oncostatin M (OSM). Growth Factors 1998;15:135-47
186. Halfter H, Postert C, Friedrich M, et al. Activation of the Jak-Stat-and MAPK-pathways by oncostatin M is not sufficient to cause growth inhibition of human glioma cells. Brain Res Mol Brain Res 2000;80:198-206
187. Halfter H, Friedrich M, Resch A, et al. Oncostatin M induces growth arrest by inhibition of Skp2, Cks1, and cyclin A expression and induced p21 expression. Cancer Res 2006;66:6530-9
188. Schrell UM, Koch HU, Marschalek R, et al. Formation of autocrine loops in human cerebral meningioma tissue by leukemia inhibitor factor, interleukin-6, and oncostatin M: inhibition of meningioma cell growth in vitro by recombinant oncostatin M. J Neurosurg 1998;88:541-8
189. Underhill-Day N, Heath JK. Oncostatin M (OSM) cytostasis of breast tumor cells: characterization of an OSM receptor beta-specific kernel. Cancer Res 2006;66:10891-901
190. Horn D, Fitzpatrick WC, Gompper PT, et al. Regulation of cell growth by recombinant oncostatin M. Growth Factors 1990;2:157-65
191. Spence MJ, Streiff R, Day D, et al. Oncostatin M induces tissue-type plasminogen activator and plasminogen activator inhibitor-1 in Calu-1 lung carcinoma cells. Cytokine 2002;18:26-34
192. Mori S, Murakami-Mori K, Bonavida B. Oncostatin M (OM) promotes the growth of DU 145 human prostate cancer cells, but not PC-3 or LNCaP, through the signaling of the OM specific receptor. Anticancer Res 1999;19:1011-15
193. Westendorf JJ, Jelinek DF. Growth regulatory pathways in myeloma. Evidence for autocrine oncostatin M expression. J Immunol 1996;157:3081-8
194. Gu ZJ, Costes V, Lu ZY, et al. Interleukin-10 is a growth factor for human myeloma cells by induction of an oncostatin M autocrine loop. Blood 1996;88:3972-86
195. Amaral MC, Miles S, Kumar G, et al. Oncostatin-M stimulates tyrosine protein phosphorylation in parallel with the activation of p42MAPK/ERK-2 in Kaposi's cells. Evidence that this pathway is important in Kaposi cell growth. J Clin Invest 1993;92:848-57
196. Miles SA, Martinez-Maza O, Rezai A, et al. Oncostatin M as a potent mitogen for AIDS-Kaposi's sarcoma-derived cells. Science 1992;255:1432-4
197. Nair BC, DeVico AL, Nakamura S, et al. Identification of a major growth factor for AIDS-Kaposi's sarcoma cells as oncostatin M. Science 1992;255:1430-2
198. David E, Tirode F, Baud'huin M, et al. Oncostatin M is a growth factor for Ewing sarcoma. Am J Pathol 2012;181:1782-95
199. Grant SL, Begley CG. The oncostatin M signalling pathway: reversing the neoplastic phenotype? Mol Med Today 1999;5:406-12
200. Gu ZJ, Zhang XG, Hallet MM, et al. A ciliary neurotrophic factor-sensitive human myeloma cell line. Exp Hematol 1996;24:1195-200
201. Weis J, Schonrock LM, Zuchner SL, et al. CNTF and its receptor subunits in human gliomas. J Neurooncol 1999;44:243-53
202. Lu J, Ksendzovsky A, Yang C, et al. CNTF receptor subunit alpha as a marker for glioma tumor-initiating cells and tumor grade. J Neurosurg 2012;117:1022-31
203. Burger R, Bakker F, Guenther A, et al. Functional significance of novel neurotrophin-1/B cell-stimulating factor-3 (cardiotrophin-like cytokine) for human myeloma cell growth and survival. Br J Haematol 2003;123:869-78
204. Pradhan A, Lambert QT, Reuther GW. Transformation of hematopoietic cells and activation of JAK2-V617F by IL-27R, a component of a heterodimeric type I cytokine receptor. Proc Natl Acad Sci USA 2007;104:18502-7
205. Yoshimoto T, Morishima N, Mizoguchi I, et al. Antiproliferative activity of IL-27 on melanoma. J Immunol 2008;180:6527-35
206. Nagai H, Oniki S, Fujiwara S, et al. Antitumor activities of interleukin-27 on melanoma. Endocr Metab Immune Disord Drug Targets 2010;10:41-6
207. Zolochevska O, Diaz-Quinones AO, Ellis J, et al. Interleukin-27 expression modifies prostate cancer cell crosstalk with bone and immune cells in vitro. J Cell Physiol 2013;228:1127-36
208. Waetzig GH, Rose-John S. Hitting a complex target: an update on interleukin-6 trans-signalling. Expert Opin Ther Targets 2012;16:225-36
209. Lu ZY, Brochier J, Wijdenes J, et al. High amounts of circulating interleukin (IL)-6 in the form of monomeric immune complexes during anti-IL-6 therapy. Towards a new methodology for measuring overall cytokine production in human in vivo. Eur J Immunol 1992;22:2819-24
210. Chevalier S, Fourcin M, Robledo O, et al. Interleukin-6 family of cytokines induced activation of different functional sites expressed by gp130 transducing protein. J Biol Chem 1996;271:14764-72
211. Gu ZJ, De Vos J, Rebouissou C, et al. Agonist anti-gp130 transducer monoclonal antibodies are human myeloma cell survival and growth factors. Leukemia 2000;14:188-97
212. Savino R, Demartis A, Ciapponi L, et al. The receptor super-antagonist Sant7. Oncol Rep 1997;4:485-92
213. Diveu C, Venereau E, Froger J, et al. Molecular and functional characterization of a soluble form of oncostatin M/interleukin-31 shared receptor. J Biol Chem 2006;281:36673-82
214. Stumhofer JS, Tait ED, Quinn WJ III, et al. A role for IL-27p28 as an antagonist of gp130-mediated signaling. Nat Immunol 2010;11:1119-26
215. Garbers C, Spudy B, Aparicio-Siegmund S, et al. An interleukin-6 receptor-dependent molecular switch mediates signal transduction of the IL-27 cytokine subunit p28 (IL-30) via a gp130 protein receptor homodimer. J Biol Chem 2013;288:4346-54
216. Dorff TB, Goldman B, Pinski JK, et al. Clinical and correlative results of SWOG S0354: a phase II trial of CNTO328 (siltuximab), a monoclonal antibody against interleukin-6, in chemotherapy-pretreated patients with castration-resistant prostate cancer. Clin Cancer Res 2010;16:3028-34
217. Xu Y, Kershaw NJ, Luo CS, et al. Crystal structure of the entire ectodomain of gp130: insights into the molecular assembly of the tall cytokine receptor complexes. J Biol Chem 2010;285:21214-18
218. Kernebeck T, Pflanz S, Muller-Newen G, et al. The signal transducer gp130: solution structure of the carboxy-terminal domain of the cytokine receptor homology region. Protein Sci 1999;8:5-12
219. Boulanger MJ, Bankovich AJ, Kortemme T, et al. Convergent mechanisms for recognition of divergent cytokines by the shared signaling receptor gp130. Mol Cell 2003;12:577-89
220. Boulanger MJ, Chow DC, Brevnova EE, et al. Hexameric structure and assembly of the interleukin-6/IL-6 alpha-receptor/gp130 complex. Science 2003;300:2101-4
221. Chow D, He X, Snow AL, et al. Structure of an extracellular gp130 cytokine receptor signaling complex. Science 2001;291:2150-5
222. Bravo J, Staunton D, Heath JK, et al. Crystal structure of a cytokine-binding region of gp130. EMBO J 1998;17:1665-74
223. Chow D, Ho J, Nguyen Pham TL, et al. In vitro reconstitution of recognition and activation complexes between interleukin-6 and gp130. Biochemistry 2001;40:7593-603