Abstract
Due to our inability to exactly characterize tumours, many patients with urinary bladder cancer undergo unnecessary surgery or cytostatic therapy. We have here studied the expression of the cytokine interleukin-1α (IL-1α) in 73 human bladder carcinomas in relation to patient survival, and examined possible relationships between IL-1α and urokinase plasminogen activator (uPA) expression. Expression levels of IL-1α and uPA mRNA were determined by RT-PCR using the quantitative TaqMan technique. The levels of IL-1α mRNA expression did not differ significantly between tumours of different grade or stage. Calculation of the overall survival rates showed a decreased overall survival time for patients with low levels of IL-1α mRNA in their tumours (log rank; P = 0.0002, median follow up: 37 months). Low tumoral IL-1α expression predicted decreased survival of patients with poorly differentiated tumours (P < 0.005) and of patients with invasive tumours (P = 0.02). uPA expression was about 4-fold increased in poorly differentiated tumours. High levels of uPA mRNA were associated with decreased overall survival times (log rank; P = 0.032, n = 60). We conclude that IL-1α is important for bladder cancer biology, and that measurements of this cytokine may be useful in pre-treatment characterization of urinary bladder cancer. © 2001 Cancer Research Campaign http://www.bjcancer.com
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Bergkvist A, Ljungqvist A and Moberger G (1965) Classification of bladder tumours based on the cellular pattern. Preliminary report of a clinical-pathological study of 300 cases with a minimum follow-up of eight years. Acta Chirurgica Scandinavica 130: 371–378
Bhat-Nakshatri P, Newton TR, Goulet R Jr and Nakshatri H (1998) NF-kappaB activation and interleukin 6 production in fibroblasts by estrogen receptor-negative breast cancer cell-derived interleukin 1alpha. Proc Natl Acad Sci USA 95: 6971–6976
Bohle A (1999) BCG’s Mechanism of action – increasing our understanding. Eur Urol 37, S1 1–8
Brinckerhoff CE, Sirum-Connolly K, Karmilowicz MJ and Auble DT (1992) Expression of stromelysin and stromelysin-2 in rabbit and human fibroblasts. Matrix 1: 165–175
Burrows FJ, Haskard DO, Hart IR, Marshall JF, Selkirk S, Poole S and Thorpe PE (1991) Influence of tumor-derived interleukin 1 on melanoma-endothelial cell interactions in vitro. Cancer Res 51: 4768–4775
Conti P, Reale M, Nicolai M, Barbacane RC, Placido FC, Iantorno R and Tenaglia R (1994) Bacillus Calmette-Guerin potentiates monocyte responses to lipopolysaccharide-induced tumor necrosis factor and interleukin-1, but not interleukin-6 in bladder cancer patients. Cancer Immunol Immunother 38: 365–371
Dinarello CA (1996) Biologic basis for interleukin-1 in disease. Blood 87: 2095–2147
Dinarello CA (1997) Interleukin-1. Cytokine Growth Factor Rev 8: 253–265
Douvdevani A, Huleihel M, Zoller M, Segal S and Apte RN (1992) Reduced tumorigenicity of fibrosarcomas which constitutively generate IL-1 alpha either spontaneously or following IL-1 alpha gene transfer. Int J Cancer 51: 822–830
Engel G, Heselmeyer K, Auer G, Bäckdahl M, Eriksson E and Linder S (1994) Correlation between stromelysin-3 mRNA level and outcome of human breast cancer. Int J Cancer 58: 830–835
Epstein JI (1998) Bladder consensus conference committee, The World Health Organization/International Society of Urological Pathology consensus classification of urothelial (translational cell) neoplasm of the urinary bladder. Am J Surg Pathol 22: 1435–148
Flamm J (1990) The value of tumor-associated tissue inflammatory reaction in primary superficial bladder cancer. Urol Res 18: 113–117
Hall RR and Prout GR (1990) Staging of bladder cancer: is the tumor, node, metastasis system adequate?. Semin Oncol 17: 517–523
Hasui Y, Marutsuka K, Suzumiya J, Kitada S, Osada Y and Sumiyoshi A (1992) The content of urokinase-type plasminogen activator antigen as a prognostic factor in urinary bladder cancer. Int J Cancer 50: 871–873
Hayashi O, Akashi M, Fujime M, Hanazawa K and Kitagawa R (1994) Detection of interleukin-1 activity in human bladder cancer cell lines. J Urol 151: 750–753
Heid CA, Stevens J, Livak KJ and Williams PM (1996) Real time quantitative PCR. Genome Research 6: 986–994
Hellsten S and Steineck G (1997) Bladder cancer in Sweden. Med Oncol 14: 141–143
Janik JE, Miller LL, Longo DL, Powers GC, Urba WJ, Kopp WC, Gause BL, Curti BD, Fenton RG, Oppenheim JJ, Conlon KC, Holmlund JT, Sznol M, Sharfman WH, Steis RG, Creekmore SP, Alvord WG, Beauchamp AE and Smith JW 2nd (1996) Phase II trial of interleukin 1 alpha and indomethacin in treatment of metastatic melanoma. J Natl Cancer Inst 88: 44–49
Jin L, Yuan RQ, Fuchs A, Yao Y, Joseph A, Schwall R, Schnitt SJ, Guida A, Hastings HM, Andres J, Turkel G, Polverini PJ, Goldberg ID and Rosen EM (1997) Expression of interleukin-1 beta in human breast carcinoma. Cancer 80: 421–434
Kaplan EL and Meier P (1955) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53: 457–481
Lamm DL (1985) Bacillus Calmette-Guerin immunotherapy for bladder cancer. J Urol 134: 40–47
Leizer T, Clarris BJ, Ash PE, van Damme J, Saklatvala J and Hamilton JA (1987) Interleukin-1 beta and interleukin-1 alpha stimulate the plasminogen activator activity and prostaglandin E2 levels of human synovial cells. Arthritis Rheum 30: 562–566
Linder C, Bystrom P, Engel G, Auer G, Aspenblad U, Strander H and Linder S (1998) Correlation between basic fibroblast growth factor immunostaining of stromal cells and stromelysin-3 mRNA expression in human breast carcinoma. Br J Cancer 77: 941–945
Liotta LA and Stetler-Stevenson WG (1993) Principles of molecular cell biology of cancer: cancer metastasis. Canc Principl & Practice of Onc 4: 134–146
Michel JB and Quertermous T (1989) Modulation of mRNA levels for urinary- and tissue-type plasminogen activator and plasminogen activator inhibitors 1 and 2 in human fibroblasts by interleukin 1. J Immunol 143: 890–895
Norioka K, Hara M, Kitani A, Hirose T, Hirose W, Harigai M, Suzuki K, Kawakami M, Tabata H, Kawagoe M and Nakamura H (1987) Inhibitory effect of human recombinant interleukin-1 alpha and beta on growth of human vascular endothelial cells. Biochem Biophys Res Commun 145: 969–975
Okada A, Bellocq JP, Rouyer N, Chenard MP, Rio MC, Chambon P and Basset P (1995) Membrane-type matrix metalloproteinase (MT- MMP) gene is expressed in stromal cells of human colon, breast, and head and neck carcinomas. Proc Natl Acad Sci USA 92: 2730–2734
Onozaki K, Matsushima K, Aggarwal BB and Oppenheim JJ (1985) Human interleukin 1 is a cytocidal factor for several tumor cell lines. J Immunol 135: 3962–3968
Pyke C, Kristensen P, Ralfkiaer E, Grondahl-Hansen J, Eriksen J, Blasi F and Dano K (1991) Urokinase-type plasminogen activator is expressed in stromal cells and its receptor in cancer cells at invasive foci in human colon adenocarcinomas. Am J Pathol 138: 1059–1067
Rothman KJ and Greenland S (eds) (1998). Modern epidemiology, 2nd ed., Lippincott-Raven: Philadelphia
SAS procedure guide, version 6. 3rd ed. (1990) SAS Institute: Cary, NC
Shipley WU, Winter KA, Kaufman DS, Lee WR, Heney NM, Tester WR, Donnelly BJ, Venner PM, Perez CA, Murray KJ, Doggett RS and True LD (1998) Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of Radiation Therapy Oncology Group 89–103. J Clin Oncol 16: 3576–3583
Sieuwerts AM, Klijn JG, Henzen-Logmans SC and Foekens JA (1999) Cytokine-regulated urokinase-type-plasminogen-activator (uPA) production by human breast fibroblasts in vitro. Breast Cancer Res Treat 55: 9–20
Stein JP, Ginsberg DA, Grossfeld GD, Chatterjee SJ, Esrig D, Dickinson MG, Groshen S, Taylor CR, Jones PA, Skinner DG and Cote R (1998) Effect of p21WAF1/CIP1 expression on tumor progression in bladder cancer. J Natl Cancer Inst 90: 1072–1079
Steineck G, Cordon-Cardo D and Scher HI (1997) Bladder and uroepithelial carcinomas. In: W Schrier, CW Gottschalk (eds), Diseases of the Kidney, pp. 803–822, Little Brown and Company: New York
Tetu B, Brisson J, Cote C, Brisson S, Potvin D and Roberge N (1993) Prognostic significance of cathepsin-D expression in node-positive breast carcinoma: an immunohistochemical study. Int J Cancer 55: 429–435
Visscher DW, DeMattia F, Ottosen S, Sarkar FH and Crissman JD (1995) Biologic and clinical significance of basic fibroblast growth factor immunostaining in breast carcinoma. Modern Pathology 8: 665–670
Voronov E, Weinstein Y, Benharroch D, Cagnano E, Ofir R, Dobkin M, White RM, Zoller M, Barak V, Segal S and Apte RN (1999) Antitumor and immunotherapeutic effects of activated invasive T lymphoma cells that display short-term interleukin 1alpha expression. Cancer Res 59: 1029–1035
Wolf C, Rouyer N, Lutz Y, Adida C, Loriot M, Bellocq J-P, Chambon P and Basset P (1993) Stromelysin 3 belongs to a subgroup of proteinases expressed in breast carcinoma fibroblastic cells and possibly implicated in tumor progression. Proc Natl Acad Sci USA 90: 1843–1847
Worth LL, Jaffe N, Benjamin RS, Papadopoulos NE, Patel S, Raymond AK, Jia SF, Rodriguez C, Gano J, Gianan MA and Kleinerman ES (1997) Phase II study of recombinant interleukin 1alpha and etoposide in patients with relapsed osteosarcoma. Clin Cancer Res 3: 1721–1729
Author information
Authors and Affiliations
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Seddighzadeh, M., Steineck, G., Jansson, O. et al. Low interleukin-1α messenger RNA levels predict decreased overall survival time of patients with urinary bladder carcinoma. Br J Cancer 84, 329–334 (2001). https://doi.org/10.1054/bjoc.2000.1584
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1054/bjoc.2000.1584
Keywords
This article is cited by
-
Expression of pigment epithelium-derived factor in bladder tumour is correlated with interleukin-8 yet not with interleukin-1α
Journal of Huazhong University of Science and Technology [Medical Sciences] (2011)