The anti-interleukin-6 antibody siltuximab down-regulates genes implicated in tumorigenesis in prostate cancer patients from a phase i study

Prostate

Volumn 71, Issue 13, 2011, Pages 1455-1465

  Karkera, Jayaprakash ^a   Steiner, Hannes ^b   Li, Weimin ^a   Skradski, Viktor ^b   Moser, Patrizia L ^c   Riethdorf, Sabine ^d   Reddy, Manjula ^a   Puchalski, Thomas ^a   Safer, Karim ^a   Prabhakar, Uma ^a,e   Pantel, Klaus ^d   Qi, Ming ^a   Culig, Zoran ^b,c  

^a CENTOCOR INC   (United States)

^b INNSBRUCK MEDICAL UNIVERSITY   (Austria)

^c MEDICAL UNIVERSITY OF INNSBRUCK   (Austria)

^d UNIVERSITY MEDICAL CENTER HAMBURG EPPENDORF   (Germany)

^e NATIONAL CANCER INSTITUTE   (United States)

Author keywords

interleukin 6; MAPK; phase I study; prostate cancer; siltuximab; STAT

Indexed keywords

2 METHYLACYL COENZYME A RACEMASE; ANDROGEN; CHROMOGRANIN A; HYDROXYSTEROID DEHYDROGENASE; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 6; INTERLEUKIN 6 RECEPTOR; INTERLEUKIN 6 RECEPTOR ALPHA; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE 1; PROTEIN P44; SILTUXIMAB; STAT PROTEIN; STAT3 PROTEIN;

ABDOMINAL PAIN; ABSENCE OF SIDE EFFECTS; ADULT; AGED; ARTICLE; CANCER PATIENT; CANCER STAGING; CARCINOGENESIS; CELL PROLIFERATION; CIRCULATING TUMOR CELL; CLINICAL ARTICLE; COMPARATIVE STUDY; CONTROLLED STUDY; CYTOLYSIS; DOWN REGULATION; DRUG DOSE ESCALATION; DRUG SAFETY; DRUG TOLERABILITY; ELECTROCHEMILUMINESCENT BASED IMMUNOASSAY; FOLLOW UP; GENE EXPRESSION; GLEASON SCORE; HUMAN; IMMUNOASSAY; IMMUNOHISTOCHEMISTRY; LUNG EMBOLISM; MALE; MAXIMUM PLASMA CONCENTRATION; MORBIDITY; OPEN STUDY; PHASE 1 CLINICAL TRIAL; PHASE 1 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROSTATE CANCER; PROSTATECTOMY; PROTEIN EXPRESSION; RHINITIS; SIGNAL TRANSDUCTION; SINGLE DRUG DOSE; URINARY TRACT INFECTION; URINE EXTRAVASATION; URINE INCONTINENCE; WOUND DEHISCENCE;

ADULT; AGED; ANTIBODIES, MONOCLONAL; CELL TRANSFORMATION, NEOPLASTIC; DOWN-REGULATION; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; IMMUNOHISTOCHEMISTRY; INTERLEUKIN-6; MALE; MIDDLE AGED; NEOPLASTIC CELLS, CIRCULATING; PROSTATIC NEOPLASMS;

EID: 79956160855     PISSN: 02704137     EISSN: 10970045     Source Type: Journal    
DOI: 10.1002/pros.21362     Document Type: Article

References (38)

1. Twillie DA, Eisenberger MA, Carducci MA, Hseih WS, Kim WY, Simons JW,. Interleukin-6: A candidate mediator of human prostate cancer morbidity. Urology 1995; 45: 542-549.
2. Hobisch A, Rogatsch H, Hittmair A, Fuchs D, Bartsch G Jr, Klocker H, Bartsch G, Culig Z,. Immunohistochemical localization of interleukin-6 and its receptor in benign, premalignant and malignant prostate tissue. J Pathol 2000; 191: 239-244. (Pubitemid 30441246)
3. Culig Z, Steiner H, Bartsch G, Hobisch A,. Interleukin-6 regulation of prostate cancer cell growth. J Cell Biochem 2005; 95: 497-505. (Pubitemid 41420180)
4. Chung TD, Yu JJ, Kong TA, Spiotto MT, Lin JM,. Interleukin-6 activates phosphatidylinositol-3 kinase, which inhibits apoptosis in human prostate cancer cell lines. Prostate 2000; 42: 1-7. (Pubitemid 30004869)
5. Steiner H, Berger AP, Godoy-Tundidor S, Bjartell A, Lilja H, Bartsch G, Hobisch A, Culig Z,. Vascular endothelial growth factor autocrine loop is established in prostate cancer cells generated after prolonged treatment with interleukin-6. Eur J Cancer 2004; 40: 1066-1072. (Pubitemid 38496265)
6. Degeorges A, Tatoud R, Fauvel Lafeve F, Podgorniak MP, Millot G, de Cremoux P, Calvo F,. Stromal cells from human benign prostate hyperplasia produce a growth-inhibitory factor for LNCaP prostate cancer cells, identified as interleukin-6. Int J Cancer 1996; 68: 207-214. (Pubitemid 26380125)
7. Wang Q, Horiatis D, Pinski J,. Interleukin-6 inhibits the growth of prostate cancer xenografts in mice by the processes of neuroendocrine differentiation. Int J Cancer 2004; 111: 508-513. (Pubitemid 39045316)
8. Hobisch A, Eder IE, Putz T, Horninger W, Bartsch G, Klocker H, Culig Z,. Interleukin-6 regulates prostate-specific protein expression in prostate carcinoma cells by activation of the androgen receptor. Cancer Res 1998; 58: 4640-4645. (Pubitemid 28480629)
9. Malinowska K, Neuwirt H, Cavarretta IT, Bektic J, Steiner H, Dietrich H, Moser PL, Fuchs D, Hobisch A, Culig Z,. Interleukin-6 stimulation of growth of prostate cancer in vitro and in vivo through activation of the androgen receptor. Endocr Relat Cancer 2009; 16: 155-169.
10. Hobisch A, Ramoner R, Fuchs D, Godoy-Tundidor S, Bartsch G, Klocker H, Culig Z,. Prostate cancer cells (LNCaP) generated after long-term interleukin-6 treatment express interleukin-6 and acquire an interleukin-6-partially resistant phenotype. Clin Cancer Res 2001; 7: 2941-2948. (Pubitemid 32911405)
11. Steiner H, Godoy-Tundidor S, Rogatsch H, Berger AP, Fuchs D, Comuzzi B, Bartsch G, Hobisch A, Culig Z,. Accelerated in vivo growth of prostate tumors that up-regulate interleukin-6 is associated with reduced retinoblastoma protein expression and activation of the mitogen-activated protein kinase pathway. Am J Pathol 2003; 162: 655-663. (Pubitemid 36267872)
12. Smith PC, Keller ET,. Anti-interleukin-6 monoclonal antibody induces regression of human prostate cancer xenografts in nude mice. Prostate 2001; 42: 88-98.
13. Zaki MH, Nemeth JA, Trikha M,. CNTO328, a monoclonal antibody to IL-6, inhibits human tumor-induced cachexia in nude mice. Int J Cancer 2001; 111: 592-595.
14. Wallner L, Dai J, Escara-Wilke J, Zhang J, Yao Z, Lu Y, Trikha M, Nemeth JA, Zaki MH, Keller ET,. Inhibition of interleukin-6 with CNTO328, an anti-interleukin-6 monoclonal antibody, inhibits conversion of androgen-dependent prostate cancer to an androgen-independent phenotype in orchiectomized mice. Cancer Res 2006; 66: 3087-3095.
15. Puchalski T, Prabhakar U, Jiao Q, Berns B, Davis HM,. Pharmacokinetic and pharmacodynamic modeling of an anti-interleukin-6 chimeric monoclonal antibody (siltuximab) in patients with metastatic renal cell carcinoma. Clin Cancer Res 2010; 16: 1652-1661.
16. Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Reuben JM, Doyle GV, Matera J, Allard WJ, Miller WC, Fritsche HA, Hortobagyi GN, Terstappen LW,. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 2004; 351: 781-791. (Pubitemid 39095313)
17. Riethdorf S, Fritsche H, Müller V, Rau T, Schindlbeck C, Rack B, Janni W, Coith C, Beck K, Jänicke F, Jackson S, Gornet S, Cristofanilli M, Pantel K,. Detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer: A validation study of the CellSearch system. Clin Cancer Res 2007; 13: 920-928. (Pubitemid 46340368)
18. Steiner H, Cavarretta IT, Moser PL, Berger AP, Bektic J, Dietrich H, Zaki MH, Nakada M, Hobisch A, Nemeth JA, Culig Z,. Regulation of growth of prostate cancer cells selected in the presence of interleukin-6 by the anti-interleukin-6 antibody CNTO 328. Prostate 2006; 66: 1744-1752. (Pubitemid 44893900)
19. Cavarretta IT, Neuwirt H, Untergasser G, Moser PL, Zaki MH, Steiner H, Rumpold H, Fuchs D, Hobisch A, Nemeth JA, Culig Z,. The antiapoptotic effect of IL-6 autocrine loop in a cellular model of advanced prostate cancer is mediated by Mcl-1. Oncogene 2007; 26: 2822-2832. (Pubitemid 46701444)
20. Dorff TB, Goldman B, Pinski JK, Mack PC, Lara PN Jr, van Veldhuizen PJ Jr, Quinn DI, Vogelzang NJ, Thompson IM Jr, Hussain MH,. 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: 3028-3034.
21. Spiotto MT, Chung TD,. STAT3 mediates IL-6-induced growth inhibition in the human prostate cancer cell line LNCaP. Prostate 2000; 42: 88-98. (Pubitemid 30056640)
22. Abdulghani J, Gu L, Dagvadorj A, Lutz J, Leiby B, Bonucelli G, Lisanti MP, Zellweger T, Alanen K, Visakorpi T, Bubendorf L, Nevalainen MT,. Stat3 promotes metastatic progression of prostate cancer. Am J Pathol 2008; 172: 1717-1728. (Pubitemid 351793362)
23. Grant WB,. Vitamin D may reduce prostate cancer metastasis by several mechanisms blocking Stat3. Am J Pathol 2008; 173: 1589-1590.
24. Cornejo MG, Kharas MG, Werneck MB, Le Bras S, Moore SA, Ball B, Beylot-Barry M, Rodig S, Aster JC, Lee BH, Cantor H, Merlio JP, Gilliland DG, Mercher T,. Constitutive JAK3 activation induces lymphoproliferative syndromes in murine bone marrow transplantation models. Blood 2009; 113: 2746-2754.
25. Giubellino A, Burke TRJ, Bottaro DP,. Grb2 signaling in cell motility and cancer. Expert Opin Ther Targets 2008; 12: 1021-1033.
26. Alam SM, Rajendran M, Ouyang S, Veeramani S, Zhang L, Lin MF,. A novel role of Shc adaptor proteins in steroid hormone-regulated cancers. Endocr Relat Cancer 2009; 16: 1-16.
27. Welsh JB, Sapinoso LM, Su AI, Kern SG, Wang-Rodriguez J, Moskaluk CA, Frierson HF Jr, Hampton GM,. Analysis of gene expression identifies candidate markers and pharmacological targets in prostate cancer. Cancer Res 2001; 61: 5974-5978. (Pubitemid 32762523)
28. Luo JH, Yu YP, Cieply K, Lin F, Deflavia P, Dhir R, Finkelstein S, Michalopoulos G, Becich M,. Gene expression analysis of prostate cancer. Mol Carcinog 2002; 33: 25-35. (Pubitemid 34052304)
29. Vanaja DK, Cheville JC, Iturria SJ, Young CY,. Transcriptional silencing of zinc finger protein 185 identified by expression profiling is associated with prostate cancer progression. Cancer Res 2003; 63: 3877-3882. (Pubitemid 36917897)
30. Lapointe J, Li C, Higgins JP, van den Rijn M, Bair E, Montgomery K, Ferrari M, Egevad L, Rayford W, Bergerheim U, Ekman P, DeMarzo AM, Tibshirani R, Botstein D, Brown PO, Brooks JD, Pollack JR,. Gene expression profiling identifies clinically relevant subtypes of prostate cancer. Proc Natl Acad Sci USA 2004; 101: 811-816. (Pubitemid 38121040)
31. Lin DW, Coleman IM, Hawley S, Huang CY, Dumpit R, Gifford D, Kezele P, Hung H, Knudsen BS, Kristal AR, Nelson PS,. Influence of surgical manipulation on prostate gene expression: Implications for molecular correlates of treatment effects and disease prognosis. J Clin Oncol 2006; 24: 3763-3770. (Pubitemid 46622315)
32. Wallace TA, Prueitt RL, Yi M, Howe TM, Gillespie JW, Yfantis HG, Stephens RM, Caporaso NE, Loffredo CA, Ambs S,. Tumor immunobiological differences in prostate cancer between African-American and European-American men. Cancer Res 2008; 68: 927-936. (Pubitemid 351206772)
33. Krongrad A, Wilson CM, Wilson JD, Allman DR, McPhaul MJ,. Androgen increases androgen receptor protein while decreasing receptor mRNA in LNCaP cells. Mol Cell Endocrinol 1991; 76: 79-88.
34. Lin DL, Whitney MC, Yao Z, Keller ET,. Interleukin-6 induces androgen responsiveness in prostate cancer cells through up-regulation of androgen receptor expression. Clin Cancer Res 2001; 7: 1773-1781. (Pubitemid 32708648)
35. Day JM, Foster PA, Tutill HJ, Parsons MF, Newmann SP, Chander SK, Allan GM, Lawrence HR, Vicker N, Potter BV, Reed MJ, Purohit A,. 17beta-dehydrogenase Type 1, and not Type 12, is a target for endocrine therapy of hormone-dependent breast cancer. Int J Cancer 2008; 122: 1931-1940. (Pubitemid 351441181)
36. Chun JY, Nadiminty N, Dutt S, Lou W, Yang JC, Kung HJ, Evans CP, Gao AC,. Interleukin-6 regulates androgen synthesis in prostate cancer cells. Clin Cancer Res 2009; 15: 4815-4822.
37. Montgomery RB, Mostaghel EA, Vessella R, Hess DL, Kalhorn TF, Higano CS, True LD, Nelson PS,. Maintenance of intratumoral androgens in metastatic prostate cancer: A mechanism for castration-resistant tumor growth. Cancer Res 2008; 68: 4447-4454.
38. Hofland J, van Weerden WM, Dits NF, Steenbergen J, van Leenders GJ, Jenster G, Schröder FH, de Jong FH,. Evidence of limited contributions for intratumoral steroidogenesis in prostate cancer. Cancer Res 2010; 70: 1256-1264.